CD44 in cancer

Critical Reviews in Clinical Laboratory Sciences

Volumn 39, Issue 6, 2002, Pages 527-579

  Naor, David ^a   Nedvetzki, Shlomo ^a   Golan, Itshak ^a   Melnik, Lora ^a   Faitelson, Yoram ^a  

^a HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

Angiogenesis; Apoptosis; Cell adhesion; Cell differentiation; Cell migration; Growth factors; Proteases; Signal transduction

Indexed keywords

ANTIBODY; CHEMOKINE; CYTOKINE; GROWTH FACTOR; HERMES ANTIGEN; PROTEINASE; LIGAND;

AMINO ACID SEQUENCE; ANGIOGENESIS; ANTIGEN PRESENTATION; APOPTOSIS; CANCER; CANCER CELL; CELL ACTIVITY; CELL ADHESION; CELL DIFFERENTIATION; CELL MEMBRANE; CELL MIGRATION; CELL PROLIFERATION; CELL SURVIVAL; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; UPREGULATION; ANIMAL; CELL COMMUNICATION; CELL MOTION; CHEMISTRY; DRUG EFFECT; IMMUNOLOGY; METABOLISM; NEOPLASM; NEOVASCULARIZATION (PATHOLOGY); PATHOLOGY; PHYSIOLOGY;

ANIMALIA;

ANIMALS; ANTIGENS, CD44; APOPTOSIS; CELL ADHESION; CELL COMMUNICATION; CELL DIFFERENTIATION; CELL MEMBRANE; CELL MOVEMENT; CELL SURVIVAL; HUMANS; LIGANDS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; SIGNAL TRANSDUCTION;

EID: 0036445586     PISSN: 10408363     EISSN: None     Source Type: Journal    
DOI: 10.1080/10408360290795574     Document Type: Review

References (282)

1. Lesley J, Hyman R, Kincade PW. CD44 and its interaction with extracellular matrix. Adv Immunol 1993; 54: 271-335.
2. Naor D, Vogt Sionov R, Ish-Shalom D. CD44: Structure, function, and association with malignant process. Adv Cancer Res 1997; 71: 241-319.
3. Lesley J, Hyman R. CD44 structure and function. Frontiers in Bioscience 1998; 3: d616-30.
4. Banerji S, Ni J, Wang S-X, et al. LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol 1999; 144: 789-801.
5. Turley EA, Noble PW, Bourguignon LYW. Signaling properties of hyaluronan receptors. J Biol Chem; in press.
6. Hofmann M, Fieber C, Assmann V, et al. Identification of IHABP, a 95 kDa intracellular hyaluronate binding protein. J Cell Sci 1998; 111: 1673-84.
7. Bajorath J. Molecular organization, structural features, and ligand binding characteristics of CD44, a highly variable cell surface glycoprotein with multiple functions. Prot Sturct Funct Genet 2000; 39: 103-11.
8. Sleeman JP, Rahmsdorf U, Steffen A, et al. CD44 variant exon v5 encodes a tyrosine that is sulphated. Eur J Biochem 1998; 255: 74-80.
9. Henke CA, Roongta U, Mickelson DJ, et al. CD44-related chondroitin sulfate proteoglycan, a cell surface receptor implicated with tumor cell invasion, mediates endothelial cell migraiton on fibrinogen and invasion into a fibrin matrix. J Clin Invest 1996; 97: 2541-52.
10. Ashkar S, Weber GF, Panoutsakopoulou V, et al. Eta-1 (Osteopontin): An early component of type-1 (cell-mediated) immunity. Science 2000; 287: 860-4.
11. Dimitroff CJ, Lee JY, Fuhlbrigge RC, et al. A distinct glycoform of CD44 is an L-selectin ligand on human hematopoietic cells. Proc Natl Acad Sci 2000; 97: 13841-6.
12. Dimitroff CJ, Lee JY, Rafii S, et al. CD44 is a major E-selectin ligand on human hematopoietic progenitor cells. J Cell Biol 2001; 153: 1277-86.
13. Lesley J, English N, Perschl A, et al. Variant cell lines selected for alterations in the function of the hyaluronan receptor CD44 show differences in glycosylation. J Exp Med 1995; 182: 431-7.
14. Hathcock KS, Hirano H, Murakami S, et al. CD44 expression on activated B cells. Differential capacity for CD44-dependent binding to hyaluronic acid. J Immunol 1993; 151: 6712-22.
15. Maiti A, Maki G, Johnson P. TNF-α induction of CD44-mediated leukocyte adhesion by sulfation. Science 1998; 282: 941-3.
16. Levesque MC, Haynes BF. Activated T lymphocytes regulate hyaluronan binding to monocyte CD44 via production of IL-2 and IFNγ. J Immunol 2001; 166: 188-96.
17. Zhang M, Singh RK, Wang MH, et al. Epidermal growth factor modulates cell attachment to hyaluronic acid by the cell surface glycoprotein CD44. Clin Exp Metastasis 1996; 14: 268-76.
18. Cichy J, Puré E. Oncostatin M and transforming growth factor-β1 induce post-translational modification and hyaluronan binding to CD44 in lung-derived epithelial tumor cells. J Biol Chem 2000; 275: 18061-9.
19. Rochman M, Moll J, Herrlich P, et al. The CD44 receptor of lymphoma cells: Structure-function relationships and mechanism of activation. Cell Adhes Commun 2000; 7:331-47.
20. Jalkanen S, Jalkanen M. Lymphocyte CD44 binds the COOH-terminal heparin-binding domain of fibronectin. J Cell Biol 1992; 116: 817-25.
21. Ehnis T, Dieterich W, Bauer M, et al. A chondroitin/dermatan sulfate form of CD44 is a receptor for collagen XIV (undulin). Exp Cell Res 1996; 229: 388-97.
22. Fassen AE, Schrager JA, Klein DJ, et al. A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type 1 collagen-mediated melanoma cell motility and invasion. J Cell Biol 1992; 116: 521-31.
23. Knutson JR, Iida J, Fields GB et al. CD44/Chondroitin sulfate proteoglycan and alpha2betal integrin mediate human melanoma cell migration on type IV collagen and invasion of basement membranes. Mol Biol Cell 1996; 7: 383-96.
24. Katagiri YU, Sleeman J, Fujii H, et al. CD44 variants but not CD44s cooperate with β1-containing intgrins to permit cells to bind to osteopontin independently of arginine-glycine-aspartic acid, thereby stimulating cell motility and chemotaxis. Cancer Res 1999; 59:219-26.
25. Sleeman JP, Kondo K, Moll J, et al. Variant exons v6 and v7 together expand the repertoire of glycosaminoglycans bound by CD44. J Biol Chem 1997; 272: 31837-44.
26. Wallach-Dayan SB, Grabovsky V, Moll J, et al. CD44-dependent lymphoma cell dissemination: A cell surface CD44 variant, rather than standard CD44, supports in vitro lymphoma cell rolling on hyaluronic acid substrate and its in vivo accumulation in the peripheral lymph nodes. J Cell Sci 2001; 114: 3463-77.
27. Sleeman J, Rudy W, Hofmann M, et al. Regulated clustering of variant CD44 proteins increases their hyaluronate binding capacity. J Cell Biol 1996; 135: 1139-50.
28. Lesley J, English N, Charles C, et al. The role of the CD44 cytoplasmic and transmembrane domains in constitutive and inducible hyaluronan binding. Eur J immunol 2000; 30: 245-53.
29. Zhu D, Bourguignon LYW. Interaction between CD44 and the repeat domain of ankyrin promotes hyaluronic acid-mediated ovarian tumor cell migration. J Cell Physiol 2000; 183: 182-95.
30. Tsukita S, Oishi K, Sato N, et al. ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons. J Cell Biol 1994; 126: 391-401.
31. Peck D, Isacke C. Hyaluronoan-dependent cell migration can be blocked by a CD44 cytoplasmic domain peptide containing a phosphoserine at position 325. J Cell Sci 1998; 111: 1595-1601.
32. Peck D, Isacke C. CD44 phosphorylation regulates melanoma cell and fibroblast migration on, but not attachment to, a hyaluronan substratum. Curr Biol 1996; 6: 884-90.
33. Terpe H-J, Stark H, Prehm P, et al. CD44 variant isoforms are preferentially expressed in basal epithelia of non-malignant human fetal and adult tissues. Histochemistry 1994; 101: 79-89.
34. McKee CM, Penno MB, Cowman M, et al. Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. J Clin Invest 1996; 98: 2403-13.
35. Ilangumaran S, Borisch B, Hoessli DC. Signal transduction via CD44: Role of plasma membrane microdomains. Leukemia and Lymphoma 1999; 35: 455-69.
36. Noble PW, McKee CM, Cowman M, et al. Hyaluronan fragments activate an NF-κBα/I-κBα autoregulatory loop in murine macrophages. J Exp Med 1996; 183: 2373-8.
37. Haegel-Kronenberger H, de la Salle H, Bohbot A, et al. Adhesive and/or signaling functions of CD44 isoforms in human dendritic cells. J Immunol 1998; 161: 3902-11.
38. Noble P, Lake F, Henson P, et al. Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-α-dependent mechanism in murine macrophages. J Clin Invest 1993; 91: 2368-77.
39. McKee CM, Lowenstein CJ, Horton MR, et al. Hyaluronan fragments induce nitric-oxide synthase in murine macrophages through a nuclear factor κB-dependent mechanism. J Biol Chem 1997; 272: 8013-8.
40. Saari H. Oxygen-derived free radicals and synovial fluid hyaluronate. Ann Rheum Dis 1991; 50: 389-92.
41. Sohara Y, Ishiguro N, Machida K, et al. Hyaluronan activates cell motility of v-Src-transformed cells via Ras-mitogen-activated protein kinase and phosphoinositide 3-Kinase-Akt in a tumor-specific manner. Mol Biol Cell 2001; 12: 1859-68.
42. Taher TEI, Smit L, Griffioen AW, et al. Signaling through CD44 is mediated by tyrosine kinases. J Biol Chem 1996; 271: 2863-7.
43. Fitzgerald KA, Bowie AG, Skeffington BS, et al. Ras, protein kinase Cζ, and IκB kinases 1 and 2 are downstream effectors of CD44 during the activation of NF-κB by hyaluronic acid fragments in T-24 carcinoma cells. J Immunol 2000; 164: 2053-63.
44. Föger N, Marhaba R, Zöller M. CD44 supports T cell proliferation and apoptosis by apposition of protein kinases. Eur J Immunol 2000; 30: 2888-99.
45. Ilangumaran S, Briol, A, Hoessli DC. CD44 selectively associates with active Src family protein tyrosine kinases Lck and Fyn in glycosphingolipid-rich plasma membrane domains of human peripheral blood lymphocytes. Blood 1998; 91: 3901-8.
46. Bourguignon LYW, Zhu H, Shao L, et al. CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton function and hyaluronic acid-dependent ovarian tumor cell migration. J Biol Chem 2001; 276: 7327-36.
47. + T cells, Int Immunol 1999; 11: 1085-92.
48. Bruno S, Fabbi M, Tiso M, et al. Cell activation via CD44 occurs in advanced stages of squamous cell carcinogenesis. Carcinogenesis 2000; 21: 893-900.
49. Bourguignon LYW, Zhu H, Shao, L, et al. CD44 interaction with Tiam1 promotes Rac1 signaling and hyaluronic acid-mediated breast tumor cell migration. J Biol Chem 2000; 275: 1829-38.
50. Kawano Y, Okamoto I, Murakami D, et al. Ras oncoprotein induces CD44 cleavage through phosphoinositide 3-OH kinase and the Rho family of small G proteins. J Biol Chem 2000; 275: 29628-35.
51. Okamoto I, Kawano Y, Matsumoto M, et al. Regulated CD44 cleavage under the control of protein kinase C, calcium influx, and the Rho family of small G proteins. J Biol Chem 1999; 274: 25525-34.
52. Oliferenko S, Kaverina I, Small JV, et al. Hyaluronic acid (HA) binding to CD44 activates Rac1 and induces lamellipodia outgrowth. J Cell Biol 2000; 148: 1159-64.
53. Shi M, Dennis K, Peschon JJ. Antibody-induced shedding of CD44 from adherent cells is linked to the assembly of the cytoskeleton. J Immunol 2001; 167: 123-31.
54. 3, 8-10-ankyrin interaction and tumor cell migration in metastatic breast cancer cells. Cell Motil Cytoskeleton 1999; 43: 269-87.
55. Morrison H, Sherman LS, Legg J, et al. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev 2001; 15: 968-80.
56. Bates RC, Edwards NS, Burns GF, et al. A CD44 survival pathway triggers chemoresistance via Lyn kinase and phosphoinositide 3-kinase/Akt in colon carcinoma cells. Cancer Res 2001; 61: 5275-83.
57. Lin Y-H, Yang-Yen H-F. The osteopontin-CD44 survival signal involves activation of the phosphatidylinositol-3-kinase/Akt signaling pathway. J Biol Chem 2001; 276: 46024-30.
58. Schmitz AAP, Govek E-E, Böttner B, et al. Rho GTPases: Signaling, migration and invasion. Exp Cell Res 2000; 261: 1-12.
59. Kozma R, Ahmed S, Best A, et al. The Ras-related protein Cdc42Hs and brandykinin protmote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts. Mol Cell Biol 1995; 15: 1942-52.
60. Nobes CD, Hall A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 1995; 81: 53-62.
61. Allen WE, Zicha D, Ridley AJ, et al. A role for Cdc42 in macrophage chemotaxis. J Cell Biol 1998; 141:1147-57.
62. Nobes CD, Hall A. Rho GTPases control polarity, protrusion, and adhesion during cell movement. J Cell Biol 1999; 144: 1235-44.
63. HER2, promotes human ovarian tumor cell activation. J Biol Chem 1997; 272: 27913-8.
64. Sherman LS, Rizvi TA, Karyala S, et al. CD44 enhances neuregulin signaling by Schwann cells. J Cell Biol 2000; 150: 1071-83.
65. Mertens G, Cassiman J-J, Van den Berghe H, et al. Cell surface heparan sulfate proteoglycans from human vascular endothelial cells. J Biol Chem 1992; 267: 20435-43.
66. Hurt-Camejo E, Rosengren B, Sartipy P, et al. CD44, a cell surface chondroitin sulfate proteoglycan, mediates binding of interferon-γ and some of its biological effects on human vascular smooth muscle cells. J Biol Chem 1999; 274: 18957-64.
67. Schlessinger J, Lax I, Lemmon M. Regulation of growth factor activation by proteoglycans: What is the role of the low affinity receptors? Cell 1995; 83: 357-60.
68. Bennett KL, Jackson DG, Simon JC, et al. CD44 isoforms containing exon v3 are responsible for presentation of heparin-binding growth factor. J Cell Biol 1995; 128: 687-98.
69. Jackson DG, Bell JI, Dickinson R, et al. Proteoglycan forms of the lymphocyte homing receptor CD44 are alternatively spliced variants containing the v3 exon. J Cell Biol 1995; 128: 673-85.
70. Greenfield B, Wang W-C, Marquardt H, et al. Characterization of the heparan sulfate and chondroitin sulfate assembly sites in CD44. J Biol Chem 1999; 274: 2511-7.
71. van der Voort R, Taher TEI, Wielenga VJM, et al. Heparan sulfate-modified CD44 promotes hepatocyte growth factor/scatter factor-induced signal transduction through the receptor tyrosine kinase c-Met. J Biol Chem 1999; 274: 6499-506.
72. Wielenga VJM, van der Voort R, Taher TEI, et al. Expression of c-Met and heparan-sulfate proteoglycan forms of CD44 in colorectal cancer. Am J Pathol 2000; 157: 1563-73.
73. van der Voort R, Keehnen RMJ, Beuling EA, et al. Regulation of cytokine signaling by B cell antigen receptor and CD40-controlled expression of heparan sulfate proteoglycans. J Exp Med 2000; 192: 1115-24.
74. Grimme HU, Termeer CC, Bennett KL, et al. Colocalization of basic fibroblast growth factor and CD44 isoforms containing the variably spliced exon v3 (CD44v3) in normal skin and in epidermal skin cancers. Br J Dermatol 1999; 141: 824-32.
75. Jones M, Tussey L, Athanasou N, et al. Heparan sulfate proteoglycan isoforms of the CD44 hyaluronan receptor induced in human inflammatory macrophages can function as paracrine regulators of fibroblast growth factor action. J Biol Chem 2000; 275: 7964-74.
76. Sherman L, Wainwright D, Ponta H, et al. A splice variant of CD44 expressed in the apical ectodermal ridge presents fibroblast growth factors to limb mesenchyme and is required for limb outgrowth. Genes Dev 1998; 12: 1058-71.
77. Tanaka Y, Adams DH, Hubscher S, et al. T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1β. Nature 1993; 361: 79-82.
78. Wolff EA, Greenfield B, Taub DD, et al. Generation of artificial proteoglycans containing glycosaminoglycan-modified CD44. Demonstration of the interaction between rantes and chondroitin sulfate. J Biol Chem 1999; 274: 2518-24.
79. Koopman G, Taher TEI, Mazzucchelli I, et al. CD44 isoforms, including the CD44 v3 variant, are expressed on endothelium, suggesting a role for CD44 in the immobilization of growth factors and the regulation of the local immune response. Biochem Biophys Res Commun 1998; 245: 172-6.
80. van der Voort R, Taher TEI, Derksen PWD, et al. The hepatocyte growth factor-Met pathway in development, tumorigenesis, and B cell differentiation. Adv Cancer Res 2000; 79: 39-90.
81. Jeffers M, Rong S, Anver M, et al. Autocrine hepatocyte growth factor/scatter factor-Met signaling induces transformation and the invasive/metastatic phenotype in C127 cells. Oncogene 1996; 13: S853-6.
82. Stetler-Stevenson WG, Aznavoorian S, Liotta LA. Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol 1993; 9: 541-73.
83. Werb Z. ECM and cell surface proteolysis: Regulating cellular ecology. Cell 1997; 91: 439-42.
84. Yu Q, Stamenkovic I. Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. Genes Dev. 1999; 13: 35-48.
85. Yu Q, Stamenkovic I. Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-β and promotes tumor invasion and angiogenesis. Genes Dev 2000; 14: 163-76.
86. Culty M, Shizari M, Thompson EW, et al. Binding and degradation of hyaluronan by human breast cancer cell lines expressing different forms of CD44: Correlation with invasive potential. J Cell Physiol 1994; 160: 275-86.
87. Liu D, Pearlman E, Diaconu E, et al. Expression of hyaluronidase by tumor cells induces angiogenesis in vivo. Proc Natl Acad Sci USA 1996; 93: 7832-7.
88. Laurent TC, Fraser JR. Hyaluronan. FASEB (Fed. Am. Exp. Biol.) J 1992; 6: 2397-404.
89. Toole BP. Hyaluronan and its binding proteins, the hyaladherins. Curr Opin Cell Biol 1990; 2: 839-44.
90. Pham HT, Block NL, Lokeshwar VB, Tumor-derived hyaluronidase: A diagnostic urine marker for high-grade bladder cancer. Cancer Res 1997; 57: 778-83.
91. Novak U, Stylli SS, Kaye AH, et al. Hyaluronidase-2 overexpression accelerates intracerebral but not subcutaneous tumor formation of murine astrocytoma cells. Cancer Res 1999; 59: 6246-50.
92. Yu Q, Toole BP, Stamenkovic I. Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function. J Exp Med 1997; 186: 1985-96.
93. De Maeyer E, De Maeyer-Guignard J. The growth rate of two transplantable murine tumors, 3LL lung carcinoma and B16F10 melanoma, is influenced by Hyal-1, a locus determining hyaluronidase levels and polymorphism. Int J Cancer 1992; 51: 657-60.
94. Takahashi K, Eto, H, Tanabe KK. Involvement of CD44 in matrix metalloproteinase-2 regulation in human melanoma cells. Int J Cancer 1999; 80: 387-95.
95. 3.8-10 is involved in cytoskeleton-mediated tumor cell migration and matrix metalloproteinase (MMP-9) association in metastatic breast cancer cells. J Cell Physiol 1998; 176: 206-15.
96. v β3. Cell 1996; 85: 683-93.
97. Ahrens T, Sleeman JP, Schempp CM, et al. Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid. Oncogene 2001; 20: 3399-408.
98. Okamoto I, Kawano Y, Tsuiki H, et al. CD44 cleavage induced by a membrane-associated metalloprotease plays a critical role in tumor cell migration. Oncogene 1999; 18: 1435-46.
99. Okamoto I, Kawano Y, Murakami D, et al. Proteolytic release of CD44 intracellular domain and its role in the CD44 signaling pathway. J Cell Biol 2001; 155: 755-62.
100. Hofmann M, Rudy W, Günthert U, et al. A link between ras and metastatic behavior of tumor cells: Ras induces CD44 promoter activity and leads to low-level expression of metastasis-specific variants of CD44 in CREF cells. Cancer Res 1993; 53: 1516-21.
101. Ishiwatari-Hayasaka H, Fujimoto T, Osawa T, et al. Requirements for signal delivery through CD44: Analysis using CD44-Fas chimeric proteins. J Immunol 1999; 163: 1258-64.
102. Fujii K, Fujii Y, Hubscher S, et al. CD44 is the physiological trigger of Fas up-regulation on rheumatoid synovial cells. J Immunol 2001; 167: 1198-203.
103. Chen D, McKallip RJ, Zeytun A, et al. CD44-deficient mice exhibit enhanced hepatitis after concanavalin A injection: Evidence for involvement of CD44 in activation-inducted cell death. J Immunol 2001; 166: 5889-97.
104. Henke C, Bitterman P, Roongta U, et al. Induction of fibroblast apoptosis by anti-CD44 antibody: Implications for the treatment of fibroproliferative lung disease. Am J Pathol 1996; 149: 1639-50.
105. Tian B, Takasu T, Henke C. Functional role of Cyclin A on induction of fibroblast apoptosis due to ligation of CD44 matrix receptor by anti-CD44 antibody. Exp Cell Res 2000; 257: 135-44.
106. Takazoe K, Tesch GH, Hill PA, et al. CD44-mediated neutrophil apoptosis in the rat. Kidney Int 2000; 58: 1920-30.
107. Yasuda M, Tanaka Y, Fujii K, et al. CD44 stimulation down-regulates Fas expression and Fas-mediated apoptosis of lung cancer cells. Int Immunol 2001; 13: 1309-19.
108. Ayroldi E, Cannarile L, Migliorati G, et al. CD44 (Pgp-1) inhibits CD3 and dexamethasone-induced apoptosis. Blood 1995; 86: 2672-8.
109. Vincent T, Jourdan M, Sy M-S, et al. Hyaluronic acid induces survival and proliferation of human myeloma cells through an interleukin-6-mediated pathway involving the phosphorylation of retinoblastoma protein. J Biol Chem 2001; 276: 14728-36.
110. Meredith JE Jr, Schwartz MA. Integrins, adhesion and apoptosis. Trends Cell Biol 1997; 7: 146-50.
111. Günthert AR, Strater J, von Reyher U, et al. Early detachment of colon carcinoma cells during CD95 (APO-1/Fas)-mediated apoptosis. I. De-adhesion from hyaluronate by shedding of CD44. J Cell Biol 1996; 134: 1089-96.
112. Bates RC, Elith CA, Thorne RF, et al. Engagement of variant CD44 confers resistance to anti-integrin antibody-mediated apoptosis in a colon carcinoma cell line. Cell Adhes Commun 1998; 6: 21-38.
113. Allouche M, Charrad RS, Bettaieb A, et al. Ligation of the CD44 adhesion molecule inhibits drug-induced apoptosis in human myeloid leukemia cells. Blood 2000; 96: 1187-90.
114. Wittig BM, Johansson B, Zöller M, et al. Abrogation of experimental colitis correlates with increased apoptosis in mice deficient for CD44 variant exon 7 (CD44v7). J Exp Med 2000; 191: 2053-63.
115. Miyake K, Medina KL, Hayashi S-I, et al. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. J Exp Med 1990; 171: 477-88.
116. Moll J, Khaldoyanidi S, Sleeman JP, et al. Two different functions for CD44 proteins in human myelopoiesis. J Clin Invest 1998; 102: 1024-34.
117. Hamann KJ, Dowling TL, Neeley SP, et al. Hyaluronic acid enchances cell prliferation during eosinopoiesis through the CD44 surface antigen. J Immunol 1995; 154: 4073-80.
118. Rafi A, Nagarkatti M, Nagarkatti PS. Hyaluronate-CD44 interactions can induce murine B-cell activation. Blood 1997; 89: 2901-8.
119. Degos L, Dombret H, Chomienne C, et al. All-trans-retinoic acid as a differentiating agent in the treatment of acute promyelocytic leukemia. Blood 1995; 85: 2643-53.
120. Charrad R-S, Li Y, Delpech B, et al. Ligation of the CD44 adhesion molecule reverses blockage of differentiation in human acute myeloid leukemia. Nature Med 1999; 5: 669-76.
121. Pepper MM. Transforming growth factor-beta: Vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev 1997; 8: 21-43.
122. West DC, Hampson IN, Arnold F, et al. Angiogenesis induced by degradation products of hyaluronic acid. Science 1985; 228: 1324-6.
123. Sattar A, Kumar S, West DC. Does hyaluronan have a role in edothelial-cell proliferation of the synovium? Semin Arthritis Rheum 1992; 22: 37-43.
124. Deed R, Rooney P, Kumar P, et al. Early-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan. Int J Cancer 1997; 71: 251-6.
125. Alpaugh ML, Lee MC, Nguyen M, et al. Myoepithelial-specific CD44 shedding contributes to the antiinvasive and antiangiogenic phenotype of myoepithelial cells. Exp Cell Res 2000; 261: 150-8.
126. Griffioen AW, Coenen MJH, Damen CA, et al. CD44 is involved in tumor angiogenesis: An activation antigen on human endothelial cells. Blood 1997; 90: 1150-9.
127. Trochon V, Mabilat C, Bertrand P, et al. Evidence of involvement of CD44 in endothelial cell proliferation, migration and angiogenesis in vitro. Int J Cancer 1996; 66: 664-8.
128. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell 1994; 76: 301-14.
129. Huttenlocher A, Sandborg RR, Horwitz AF. Adhesion in cell migration. Curr Opin Cell Biol 1995; 7: 697-706.
130. Friedl P, Maaser K, Klein CE, et al. Migration of highly aggressive MV3 melanoma cells in 3-dimensional collagen lattices results in local matrix reorganization and shedding of α2 and β1 integrins and CD44. Cancer Res 1997; 57: 2061-70.
131. Svoe K, White J, Valliant P, et al. Acute lung injury fibroblast migration and invasion of a fibrin matrix is mediated by CD44. J Clin Invest 1996; 98: 1713-27.
132. Zohar R, Suzuki N, Suzuki K, et al. Intracellular osteopontin is an integral component of the CD44-ERM complex involved in cell migration. J Cell Physiol 2000; 184: 118-30.
133. Sheikh H, Legg J, Lewis C, et al. Discrete domains within the hyaluronan receptor CD44 regulate membrane localization and cell migration. Cell Adhes Commun 1998; 6: 149-56.
134. 2+/calmodulin-dependent protein kinase mediates the phosphorylation of CD44 required for cell migration on hyaluronan. Biochem J 2001; 357: 843-50.
135. Thomas L, Byers HR, Vink J, et al. CD44H regulates tumor cell migration on hyaluronate-coated substrate. J Cell Biol 1992; 118: 971-7.
136. Tanimura S, Chatani Y, Hoshino R, et al. Activation of the 41/43 kDa mitogen-activated protein kinase signaling pathway is required for hepatocyte growth factor-induced cell scattering. Oncogene 1998; 17: 57-65.
137. Khwaja A, Lehmann K, Marte BM, et al. Phosphoinositide 3-kinase induces scattering and tubulogenesis in epithelial cells through a novel pathway. J Biol Chem 1998; 273: 18793-801.
138. Potempa S, Ridley AJ. Activation of both MAP kinase and phosphatidylinositide 3-kinase by Ras is required for hepatocyte growth factor/scatter factor-induced adherens junction disassembly. Mol Biol Cell 1998; 9: 2185-200.
139. DeGrendele HC, Estess P, Picker LJ, et al. CD44 and its ligand hyaluronate mediate rolling under physiologic flow: A novel lymphocyte-endothelial cell primary adhesion pathway. J Exp Med 1996; 183: 1119-30.
140. DeGrendele HC, Kosfiszer M, Estess P, et al. CD44 activation and associated primary adhesion is inducible via T cell receptor stimulation. J Immunol 1997; 159: 2549-53.
141. DeGrendele HC, Estess P, Siegelman MH. Requirement for CD44 in activated T cell extravasation into an inflammatory site. Science 1997; 278: 672-5.
142. Mohamadzadeh M, DeGrendele H, Arizpe H, et al. Proinflammatory stimuli regulate endothelial hyaluronan expression and CD44/HA-dependent primary adhesion. J Clin Invest 1998; 101: 97-108.
143. Estess P, Nandi A, Mohamadzadeh M, et al. Interleuken 15 induces endothelial hyaluronan expression in vitro and promotes activated T cell extravasation through a CD44-dependent pathway in vivo. J Exp Med 1999; 190: 9-19.
144. Nandi A, Estess P, Siegelman MH. Hyaluronan anchoring and regulation on the surface of vascular endothelial cells is mediated through the functionally active form of CD44. J Biol Chem 2000; 275: 14939-48.
145. Warnock RA, Askari S, Butcher EC, et al. Molecular mechansims of lymphocyte homing to peripheral lymph nodes. J Exp Med 1998; 187: 205-16.
146. Siegelman MH, Stanescu D, Estess P. The CD44-initiated pathway of T-cell extravasation uses VLA-4 but not LFA-1 for firm adhesion. J Clin Invest 2000; 105: 683-91.
147. Fujisaki T, Tanaka Y, Fujii K, et al. CD44 stimulation induces integrin-mediated adhesion of colon cancer cell lines to endothelial cells by upregulation of integrins and c-Met and activation of integrins. Cancer Res 1999; 59: 4427-34.
148. Clark RA, Alon R, Springer TA. CD44 and hyaluronan-dependent rolling interactions of lymphocytes on tonsillar stroma. J Cell Biol 1996; 134: 1075-87.
149. Estess P, DeGrendele HC, Pascual V, et al. Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity. J Clin Invest 1998; 102: 1173-82.
150. Iida N, Bourguignon LYW. Coexpression of CD44 variant (v10/ex14) and CD44s in human mammary epithelial cell promotes tumorigenesis. J Cell Physiol 1997; 171: 152-60.
151. + lymphoma cells in lymphoid organs. Int J Cancer 1997; 71: 462-9.
152. Günthert U, Hofmann M, Rudy W, et al. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell 1991; 65: 13-24.
153. Weiss JM, Renkl AC, Sleeman J, et al. CD44 variant isoforms are essential for the function of epidermal Langerhans cells and dendritic cells. Cell Adhes Commun 1998; 6: 157-60.
154. Siegelman MH, DeGrendele HC, Estess P. Activation and interaction of CD44 and hyaluronan in immunological systems. J Leukoc Biol 1999; 66: 315-21.
155. Aziz KA, Till KJ, Zuzel M, et al. Invovlement of CD44-hyaluronan interaction in malignant cell homing and fibronectin sythesis in hairy cell leukemia. Blood 2000; 96: 3161-7.
156. Duband JL, Nuckolls GH, Ishihara A, et al. Fibronectin receptor exhibits high lateral mobility in embryonic locomoting cells but is immobile in focal contacts and fibrillar streaks in stationary cells. J Cell Biol 1988; 107: 1385-96.
157. Lauffenburger DA. Models for receptor-mediated cell phenomena: Adhesion and migration. Annu Rev Biophys Chem 1991; 20: 387-414.
158. DiMilla PA, Stone JA, Quinn JA, et al. Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength. J Cell Biol 1993; 122: 729-37.
159. Asosingh K, Günthert U, Bakkus MHC, et al. In vivo induction of insulin-like growth factor-I receptor and CD44v6 confers homing and adhesion to murine multiple myeloma cells. Cancer Res 2000; 60: 3096-104.
160. Sy MS, Guo Y-J, Stamenkovic I. Distinct effects of two CD44 isoforms on tumor growth in vivo. J Exp Med 1991; 174: 859-66.
161. Bartolazzi A, Peach R, Aruffo A, et al. Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development. J Exp Med 1994; 180: 53-66.
162. Bartolazzi A, Jackson D, Bennett K, et al. Regulation of growth and dissemination of a human lymphoma by CD44 splice variants. J Cell Sci 1995; 108: 1723-33.
163. Kogerman P, Sy M-S, Culp LA. Overexpressed human CD44s promotes lung colonization during micrometastasis of murine fibrosarcoma cells: Facilitated retention in the lung vasculature. Proc Natl Acad Sci USA 1997; 94: 13233-8.
164. Yakushijin Y, Steckel J, Kharbanda S, et al. A directly spliced exon 10-containing CD44 variant promotes the metastasis and homotypic aggregation of aggressive non-Hodgkin's lymphoma. Blood 1998; 91: 4282-91.
165. Choi SH, Takahashi K, Eto H, et al. CD44s expression in human colon carcinomas influences growth of liver metastases. Int J Cancer 2000; 85: 523-6.
166. Screaton GR, Bell MV, Bell JI, et al. The identification of a new alternative exon with highly restricted tissue expression in transcripts encoding the mouse Pgp-1 (CD44) homing receptor. J Biol Chem 1993; 268: 12235-8.
167. Sleeman JP, Arming S, Moll JF, et al. Hyaluronate-independent metastatic behavior of CD44 variant-expressing pancreatic carcinoma cells. Cancer Res 1996; 56: 3134-41.
168. Seiter S, Arch R, Reber S, et al. Prevention of tumor metastasis formation by anti-variant CD44. J Exp Med 1993; 177: 443-55.
169. Zawadzki V, Perschl A, Rösel, M, et al. Blockage of metastasis formation by CD44-receptor globulin. Int J Cancer 1998; 75: 919-24.
170. Breyer R, Hussein S, Radu DL, et al. Disruption of intracerebral progression of C6 rat glioblastoma by in vivo treatment with anti-CD44 monoclonal antibody. J Neurosurg 2000; 92: 140-9.
171. Zahalka MA, Okon E, Gosslar U, et al. Lymph node (but not spleen) invasion by murine lymphoma is both CD44- and hyaluronate-dependent. J Immunol 1995; 154: 5345-55.
172. Strobel T, Swanson L, Cannistra SA. In vivo inhibition of CD44 limits intra-abdominal spread of a human ovarian cancer xenograft in nude mice: A novel role for CD44 in the process of peritoneal implantation. Cancer Res 1997; 57: 1228-32.
173. Guo Y, Ma J, Wang J, et al. Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody. Cancer Res 1994; 54: 1561-5.
174. 99mTechnetium-labeled anti-CD44v6 monoclonal antibody BIWA 1 in head and neck cancer patients. Clin Cancer Res 2000; 6: 3046-55.
175. Zeng C, Toole BP, Kinney SD, et al. Inhibition of tumor growth in vivo by hyaluronan oligomers. Int J Cancer 1998; 77: 396-401.
176. Sy M-S, Guo Y-J, Stamenkovic I. Inhibition of tumor growth in vivo with a soluble CD44-immunoglobulin fusion protein. J Exp Med 1992; 176: 623-7.
177. Brinck J, Heldin P. Expression of recombinant hyaluronan synthase (HAS) isoforms in CHO cells reduces cell migration and cell surface CD44. Exp Cell Res 1999; 252: 342-51.
178. Harada N, Mizoi T, Kinouchi M, et al. Introduction of antisense CD44s
179. Reeder JA, Gotley DC, Walsh MD, et al. Expression of antisense CD44 variant 6 inhibits colorectal tumor metastasis and tumor growth in a wound environment. Cancer Res 1998; 58: 3719-26.
180. Hekele A, Dall P, Moritz D, et al. Growth retardation of tumors by adoptive transfer of cytotoxic T lymphocytes reprogrammed by CD44v6-specific SCFV: ζ-chimera. Int J Cancer 1996; 68: 232-8.
181. Yu Q, Toole BP. A new alternatively spliced exon between v9 and v10 provides a molecular basis for synthesis of soluble CD44. J Biol Chem 1996; 271: 20603-7.
182. Campanero MR, Pulido R, Alonso JL, et al. Down-regulation by tumor necrosis factor-α of neutrophil cell surface expression of the sialophorin CD43 and the hyaluronate receptor CD44 through a proteolytic mechanism. Eur J Immunol 1991; 21: 3045-8.
183. Ba∼il V, Hořejší V. Shedding of the CD44 adhesion molecule from leukocytes induced by anti-CD44 monoclonal antibody simulating the effect of a natural receptor ligand. J Immnunol 1992; 149: 747-53.
184. Katoh S, McCarthy JB, Kincade PW. Characterization of soluble CD44 in the circulation of mice. Levels are affected by immune activity and tumor growth. J Immunol 1994; 153: 3440-9.
185. Guo YJ, Liu G, Wang X, et al. Potential use of soluble CD44 in serum as indicator of tumor burden and metastasis in patients with gastric or colon cancer. Cancer Res 1994; 54: 422-6.
186. Martin S, Jansen F, Bokelmann J, et al. Soluble CD44 splice variants in metastasizing human breast cancer. Int J Cancer 1997; 74: 443-5.
187. Kittl EM, Ruckser R, Selleny S, et al. Evaluation of soluble CD44 splice variant v5 in the diagnosis and follow-up in breast cancer patients. Exp Clin Immunogenet 1997; 14: 264-72.
188. Ristamäki R, Joensuu H, Grön-Virta K, et al. Origin and function of circulating CD44 in non-Hodgkin's lymphoma. J Immunol 1997; 158: 3000-8.
189. Ristamäki R, Joensuu H, Jalkanen S. Serum CD44 in non-Hodgkin's lymphoma. Leukemia and Lymphoma 1999; 33: 433-40.
190. Mäenpää H, Ristamäki R, Virtamo J, et al. Serum CD44 levels preceding the diagnosis of non-Hodgkin's lymphoma. Leukemia and Lymphoma 2000; 37: 585-92.
191. Beksaç M, Arat M, Akan H, et al. Circulating CD44 and intercellular adhesion molecule-1 levels in low-grade non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia patients during interferon-α-2a treatment. Cancer 2000; 89: 1474-81.
192. Sasaki K, Niitsu N. Elevated serum levels of soluble CD44 variant 6 are correlated with shorter survival in aggressive non-Hodgkin's lymphoma. Eur J Haematol 2000; 65: 195-202.
193. Navarro J-T, Ribera J-M, Vaquero M, et al. Increased serum levels of CD44s and CD44v6 in patients with AIDS-related non-Hodkin's lymphoma. AIDS 2000; 14: 1460-1.
194. De Rossi G, Marroni P, Paganuzzi M, et al. Increased serum levels of soluble CD44 standard, but not of variant isoforms v5 and v6, in B cell chronic lymphocytic leukemia. Leukemia 1997; 11: 134-41.
195. Molica S, Vitelli G, Levato D, et al. Elevated serum levels of soluble CD44 can identify a subgroup of patients with early B-cell chronic lymphocytic leukemia who are at high risk of disease progression. Cancer 2001; 92: 713-9.
196. Takeuchi M, Tanizawa A, Fukumoto Y, et al. Serum soluble CD44 in pediatric patients with acute leukemia. J Pediatr Hematol Oncol 1999; 21: 384-8.
197. Yokota A, Ishii G, Sugaya Y, et al. Potential use of serum CD44 as an indicator of tumour progression in acute leukemia. Hematol Oncol 1999; 17: 161-8.
198. Gadducci A, Ferdeghini M, Fanucchi A, et al. Serum assay of soluble CD44 standard (sCD44-st), CD44 splice variant v5 (sCD44-v5), and CD44 splice variant v6 (sCD44-v6) in patients with epithelial ovarian cancer. Anticancer Res 1997; 17: 4463-6.
199. Zeimet AG, Widschwendter M, Uhl Steidl M, et al. High serum levels of soluble CD44 variant isoform v5 are associated with favourable clinical outcome in ovarian cancer. Br J Cancer 1997; 76: 1646-51.
200. Peterson RM, Yu Q, Stamenkovic I, et al. Perturbation of hyaloronan interactions by soluble CD44 inhibits growth of murine mammary carcinoma cells in ascites. Am J Pathol 2000; 156: 2159-67.
201. Goodison S, Tarin D. Current status of CD44 variant isoforms as cancer diagnostic makers. Histopathology 1998; 32: 1-6.
202. Sugiyama M, Woodman A, Sugino T, et al. Non-invasive detection of bladder cancer by identification of abnormal CD44 proteins in exfoliated cancer cells in urine. J Clin Pathol Mol Pathol 1995; 48: M142-7.
203. Woodman AC, Goodison S, Drake M, et al. Noninvasive diagnosis of bladder carcinoma by enzyme-linked immunosorbent assay detection of CD44 isoforms in exfoliated urothelia. Clin Cancer Res 2000; 6: 2381-92.
204. Yoshida K, Bolodeoku, J, Sugino T, et al. Abnormal retention of intron 9 in CD44 gene transcripts in human gastrointestinal tumors. Cancer Res 1995; 55: 4273-7.
205. Matsumura Y, Sugiyama M, Matsumura S, et al. Unusual retention of introns in CD44 gene transcripts in bladder cancer provides new diagnostic and clinical oncological opportunities. J Pathol 1995; 177: 11-20.
206. Bànkfalvi À, Terpe H-J, Breukelmann D, et al. Gains and losses of CD44 expression during breast carcinogenesis and tumour progression. Histopathology 1998; 33: 107-16.
207. Bànkfalvi À, Terpe H-J, Breukelmann D, et al. Immunophenotypic and prognostic analysis of E-cadherin and β-catenin expression during breast carcinogenesis and tumour progression: A comparative study with CD44. Histopathology 1999; 34: 25-34.
208. Herrera-Gayol A, Jothy S. Adhesion proteins in the biology of breast cancer: Contribution of CD44. Exp Mol Pathol 1999; 66: 149-56.
209. Mikami T, Mitomi H, Hara A, et al. Decreased expression CD44, alpha-catenin, and deleted colon carcinoma and altered expression of beta-catenin in ulcerative colitis-associated dysplasia and carcinoma, as compared with sporadic colon neoplasms. Cancer 2000; 89: 733-40.
210. Ishida T. Immunohistochemical expression of the CD44 variant 6 in colorectal adenocarcinoma. Surg Today 2000; 30: 28-32.
211. Friedrichs K, Franke F, Lisboa B-W, et al. CD44 isoforms correlate with cellular differentiation but not with prognosis in human breast cancer. Cancer Res 1995; 55: 5424-33.
212. Koyama S, Maruyama T, Adachi S. Expression of epidermal growth factor receptor and CD44 splicing variants sharing exons 6 and 9 on gastric and esophageal carcinomas: A two-color flow-cytometric analysis. J Cancer Res Clin Oncol 1999; 125: 47-54.
213. Southgate J, Trejdosiewicz LK, Smith B, et al. Patterns of splice variant CD44 expression by normal human urothelium in situ and in vitro and by bladder-carcinoma cell lines. Int J Cancer 1995; 62: 449-56.
214. Hong R-L, Pu Y-S, Hsieh T-S, et al. Expressions of E-Cadherin and exon v6-containing isoforms of CD44 and their prognostic values in human transitional cell carcinoma. J Urol 1995; 153: 2025-8.
215. Gasbarri A, Martegani MP, Del Prete F, et al. Galectin-3 and CD44v6 isoforms in the preoperative evaluation of thyroid nodules. J Clin Oncol 1999; 17: 3494-502.
216. Böhm, JP, Niskanen LK, Pirinen RT, et al. Reduced CD44 standard expression is associated with tumour recurrence and unfavourable outcome in differentiated thyroid carcinoma. J Pathol 2000; 192: 321-7.
217. Mizera-Nyczak E, Dyszkiewicz W, Heider K-H, et al. Isoform expression of CD44 adhesion molecules, Bcl-2, p53 and Ki-67 proteins in lung cancer. Tumor Biol 2001; 22: 45-53.
218. Endo K, Terada T. Protein expression of CD44 (standard and variant isoforms) in hepatocellular carcinoma: Relationships with tumor grade, clinicopathological parameters, p53 expression, and patient survival. J Hepatol 2000; 32: 78-84.
219. Paradis V, Ferlicot S, Ghannam E, et al. CD44 is an independent prognostic factor in conventional renal cell carcinomas. J Urol 1999; 161: 1984-7.
220. Daniel L, Lechevallier E, Giorgi R, et al. CD44s and CD44v6 expression in localized T1-T2 conventional renal cell carcinomas. J Pathol 2001; 193: 345-9.
221. Yanagisawa N, Mikami T, Mitomi H, et al. CD44 variant overexpression in gallbladder carcinoma associated with tumor dedifferentiation. Cancer 2001; 91: 408-16.
222. Rodríguez-Rodríguez L, Sancho-Torres I, Leakey P, et al. CD44 splice variant expression in clear cell carcinoma of the ovary. Gynecol Oncol 1998; 71: 223-9.
223. Saegusa M, Machida D, Hashimura M, et al. CD44 expression in benign, premalignant, and malignant ovarian neoplasms: Relation to tumour development and progression. J Pathol 1999; 189: 326-37.
224. Sancho-Torres I, Mesonero C, Miller Watelet J-L, et al. Clear cell carcinoma of the ovary: Characterization of its CD44 isoform repertoire. Gynecol Oncol 2000; 79: 187-95.
225. Katsura M, Furumoto H, Nishimura M, et al. Overexpression of CD44 variants 6 and 7 in human endometrial cancer. Gynecol Oncol 1998; 71: 185-9.
226. Schaider H, Soyer HP, Heider K-H, et al. CD44 and variants in melanocytic skin neoplasms. J Cutan Pathol 1998; 25: 199-203.
227. Berner HS, Davidson B, Berner A, et al. Differential expression of CD44s and CD44v3-10 in adenocarcinoma cells and reactive mesothelial cells in effusions. Virchows Arch 2000; 436: 330-5.
228. Wielenga VJM, Heider K-H, Offerhaus GJA, et al. Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res 1993; 53: 4754-6.
229. Orzechowski H-D, Beckenbach C, Herbst H, et al. Expression of CD44v6 is associated with cellular dysplasia in colorectal epithelial cells. Eur J Cancer 1995; 31A: 2073-9.
230. Sumiyoshi Y, Yamashita Y, Maekawa T, et al. Expression of CD44, vascular endothelial growth factor, and proliferating cell nuclear antigen in severe venous invasional colorectal cancer and its relationship to liver metastasis. Surg Today 2000; 30: 323-7.
231. Finke LH, Terpe H-J, Zörb C, et al. Colorectal cancer prognosis and expression of exon-v6-containing CD44 proteins. Lancet 1995; 345: 583.
232. Jackson PA, Green MA, Pouli A, et al. Relation between stage, grade, proliferation, and expression of p53 and CD44 in adenomas and carcinomas of the colorectum. J Clin Pathol 1995; 48: 1098-101.
233. Asao T, Nakamura J, Shitara Y, et al. Loss of standard type of CD44 expression in invaded area as a good indicator of lymph-node metastasis in colorectal carcinoma. Dis Colon Rectum 2000; 43: 1250-5.
234. Imazeki F, Yokosuka O, Yamaguchi T, et al. Expression of variant CD44-messenger RNA in colorectal adenocarcinomas and adenomatous polyps in humans. Gastroenterology 1996; 110: 362-8.
235. Manten-Horst E, Danen EH, Smit L, et al. Expression of CD44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential. Int J Cancer 1995; 64: 182-8.
236. Kurozumi K, Nakao K, Nishida T, et al. Significance of biologic aggressiveness and proliferating activity in papillary thyroid carcinoma. World J Surg 1998; 22: 1237-42.
237. de Alava E, Panizo A, Sola I, et al. CD44v6 expression is related to progression in renal epithelial tumors. Histopathology 1998; 33: 39-45.
238. Tsuji NLM, Kanda K, Murakami Y, et al. Analysis of CD44 isoform v10 expression and its prognostic value in renal cell carcinoma. BJU Intl 2000; 85: 514-8.
239. Dall P, Heider K-H, Sinn H-P, et al Comparison of immunohistochemistry and RT-PCR for detection of CD44v-expression, a new prognostic factor in human breast cancer. Int J Cancer 1995; 60: 471-7.
240. Sinn H-P, Heider K-H, Skroch-Angel P, et al. Human mammary carcinomas express homologues of rat metastasis-associated variants of CD44. Breast Cancer Res Treat 1995; 36: 307-13.
241. Kanke M, Fujii M, Kameyama K, et al. Role of CD44 variant exon 6 in invasion of head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2000; 126: 1217-23.
242. Sato S, Miyauchi M, Takekoshi T, et al. Reduced expression of CD44 variant 9 is related to lymph node metastasis and poor survival in squamous cell carcinoma of tongue. Oral Oncol. 2000; 36: 545-9.
243. Pirinen R, Hirvikoski P, Böhm J, et al. Reduced expression of CD44v3 variant isoform is associated with unfavorable outcome in non-small cell lung carcinoma. Hum Pathol 2000; 31: 1088-95.
244. Yokoyama Y, Hiyama E, Murakami Y, et al. Lack of CD44 variant 6 expression in advanced extrahepatic bile duct/ampullary carcinoma. Cancer 1999; 86: 1691-9.
245. De Marzo AM, Bradshaw C, Sauvageot J, et al. CD44 and CD44v6 downregulation in clinical prostatic carcinoma: Relation to Gleason grade and cytoarchitecture. Prostate 1998; 34: 162-8.
246. Aaltomaa S, Lipponen P, Ala-Opas M, et al. Expression and prognostic value of CD44 standard and variant v3 and v6 isoforms in prostate cancer. Eur Urol 2001; 39: 138-44.
247. Kallakury BVS, Yang F, Figge J, et al. Decreased levels of CD44 protein and mRNA in prostate carcinoma: Correlation with tumor grade and ploidy. Cancer 1996; 78: 1461-9.
248. Noordzij MA, Steenbrugge G-J V, Verkaik NS, et al. The prognostic value of CD44 isoforms in prostate cancer patients treated by radical prostatectomy. Clin Cancer Res 1997; 3: 805-15.
249. Paradis V, Eschwège P, Loric S, et al. De novo expression of CD44 in prostate carcinoma is correlated with systemic dissemination of prostate cancer. J Clin Pathol 1998; 51: 798-802.
250. 1. Cancer Res 1997; 57: 846-9.
251. Lou W, Krill D, Dhir R, et al. Methylation of the CD44 metastasis suppressor gene in human prostate cancer. Cancer Res 1999; 59: 2329-31.
252. Verkaik NS, van Steenbrugge GJ, van Weerden WM, et al. Silencing of CD44 expression in prostate cancer by hypermethylation of the CD44 promoter region. Lab Invest 2000; 80: 1291-8.
253. Kito H, Suzuki H, Ichikawa T, et al. Hypermethylation of the CD44 gene is associated with progression and metastasis of human prostate cancer. Prostate 2001; 49: 110-5.
254. Yamamichi K, Uehara Y, Kitamura N, et al. Increased expression of CD44v6 mRNA significantly correlates with distant metastasis and poor prognosis in gastric cancer. Int J Cancer 1998; 79: 256-62.
255. Tempfer C, Sliutz G, Haeusler G, et al. CD44v3 and v6 variant isoform expression correlates with poor prognosis in early-stage vulvar cancer. Br J Cancer 1998; 78: 1091-4.
256. Kuryu M, Ozaki T, Nishida K, et al. Expression of CD44 variants in osteosarcoma. J Cancer Res Clin Oncol 1999; 125: 646-52.
257. Stoll C, Baretton G, Soost F, et al. Prognositc importance of the expression of CD44 splice variants in oral squamous cell carcinomas. Oral Oncol 1999; 35: 484-9.
258. Gotoda T, Matsumura Y, Kondo H, et al. Expression of CD44 variants and prognosis in oesophageal squamous cell carcinoma. Gut 2000; 46: 14-9.
259. Ayhan A, Tok EC, Bildirici I, et al. Overexpression of CD44 variant 6 in human endometrial cancer and its prognositic significance. Gynecol Oncol 2001; 80: 355-8.
260. Karjalainen JM, Tammi RH, Tammi MI, et al. Reduced level of CD44 and hyaluronan associated with unfavorable prognosis in clinical stage 1 cutaneous melanoma. Am J Pathol 2000; 157: 957-65.
261. Setälä L, Lipponen P, Tammi R, et al. Expression of CD44 and its variant isoform v3 has no prognostic value in gastric cancer. Histopathology 2001; 38: 13-20.
262. Sneath RJ, Mangham DC. CD44 isoform expression in synovial sarcoma correlates with epitheliogenesis but not prognosis. Histopathology 2000; 37: 166-74.
263. Hirata T, Fukuse T, Naiki H, et al. Expression of CD44 variant exon 6 in stage I non-small cell lung carcinoma as a prognostic factor. Cancer Res 1998; 58: 1108-10.
264. Kahara N, Ozaki T, Doi T, et al. CD44 expression in soft tissue sarcomas. Virchows Arch 2000; 436: 574-8.
265. Maula S, Huuhtanen RL, Blomqvist CP, et al. The adhesion molecule CD44v6 is associated with a high risk for local recurrence in adult soft tissue sarcomas. Br J Cancer 2001; 84: 244-52.
266. Yamaguchi A, Urano T, Goi T, et al. Expression of a CD44 variant containing exons 8 to 10 is a useful-independent factor for the prediction of prognosis in colorectal cancer patients. J Clin Oncol 1996; 14: 1122-7.
267. Mulder J-W R, Kruyt PM, Sewnath M, et al. Colorectal cancer prognosis and expression of exon-v6 containing CD44 proteins. Lancet 1994; 344: 1470-2.
268. Mayer B, Jauch KW, Günthert U, et al. De novo expression of CD44 and survival in gastric cancer. Lancet 1993; 342: 1019-22.
269. Koretz K, Möller P, Lehnert T, et al. Effect of CD44v6 on survival in colorectal carcinoma. Lancet 1995; 345: 327-8.
270. Hong R-L, Lee W-J, Shun C-T, et al. Expression of CD44 and its clinical implication in diffuse-type and intestinal-type gastric adenocarcinomas. Oncology 1995; 52: 334-9.
271. Lipponen P, Aaltoma S, Kosma V-M, et al. Expression of CD44 standard and variant-v6 proteins in transitional cell bladder tumours and their relation to prognosis during a long-term follow-up. J Pathol 1998; 186: 157-64.
272. Toma V, Hauri D, Schmid U, et al. Focal Loss of CD44 variant protein expression is related to recurrence in superficial bladder carcinoma. Am J Pathol 1999; 155: 1427-32.
273. Aaltomaa S, Lipponen P, Viitanen J, et al. Prognostic value of CD44 standard, variant isoforms 3 and 6 and α-catenin expression in local prostate cancer treated by radical prostatectomy. Eur Urol 2000; 38: 555-62.
274. Costa S, Terzano P, Bovicelli A, et al. CD44 isoform 6 (CD44v6) is a prognostic indicator of the response to neoadjuvant chemotherapy in cervical carcinoma. Gynecol Oncol 2001; 80: 67-73.
275. Kaufmann M, Heider K-H, Sinn H-P, et al. CD44 variant exon epitopes in primary breast cancer and length of survival. Lancet 1995; 345: 615-19.
276. Friedrichs K, Kügler G, Franke F, et al. CD44 isoforms in prognosis of breast cancer. Lancet 1995; 345: 1237.
277. Foekens JA, Dall P, Klijn JGM, et al. Prognostic value of CD44 variant expression in primary breast cancer. Int J Cancer 1999; 84: 209-15.
278. Gilcrease MZ, Guzman-Paz M, Niehans G, et al. Correlation of CD44s expression in renal clear cell carcinomas with subsequent tumor progression or recurrence. Cancer 1999; 86: 2320-6.
279. Stauder R, Eisterer W, Thaler J, et al. CD44 variant isoforms in non-Hodgkin's lymphoma: A new independent prognostic factor. Blood 1995; 85: 2885-99.
280. Ristamäki R, Joensuu H, Söderström K-O, et al. CD44v6 expression in non-Hodgkin's lymphoma: An association with low histological grade and poor prognosis. J Pathol 1995; 176: 259-67.
281. Cywes C, Wessels MR. Group A Streptococcus tissue invasion by CD44-mediated cell signaling. Nature 2001; 414: 648-52.
282. van Weering DHJ, Baas PD, Bos JL. A PCR-based method for the analysis of human CD44 splice products. PCR Methods Appl 1993; 3: 100-6.