Glycomechanics of the metastatic cascade: Tumor cell-endothelial cell interactions in the circulation

Annals of Biomedical Engineering

Volumn 40, Issue 4, 2012, Pages 790-805

  Geng, Yue ^a   Marshall, Jocelyn R ^a   King, Michael R ^a  

^a Cornell University   (United States)

Author keywords

Adhesion; Bloodstream; Cancer; Glycomechanics; Metastasis

Indexed keywords

ADHESION MOLECULES; BLOODSTREAM; CANCER; CANCER CELLS; CELL ADHESION FORCE; CELL INTERACTION; CIRCULATING TUMOR CELLS; CIRCULATORY SYSTEMS; COMPUTATIONAL APPROACH; FLUID SHEAR STRESS; GLYCOMECHANICS; HYDRODYNAMIC SHEAR FORCES; LEUKOCYTE ADHESION; MECHANICAL FORCE; METASTASIS; MICROVILLI; SELECTINS; TUMOR SITE;

CELL ADHESION; CELL MEMBRANES; DISEASES; ENDOTHELIAL CELLS; FLUID MECHANICS; GLYCOPROTEINS; INDUSTRY; LIGANDS; PATHOLOGY; TUMORS;

ADHESION;

CELL ADHESION MOLECULE; MUC1 PROTEIN, HUMAN; MUCIN 1;

ANIMAL; BIOSYNTHESIS; CELL ADHESION; CELL COMMUNICATION; ENDOTHELIUM CELL; GENE EXPRESSION REGULATION; HUMAN; METABOLISM; PATHOLOGY; REVIEW; TRANSENDOTHELIAL AND TRANSEPITHELIAL MIGRATION; TUMOR EMBOLISM;

ANIMALS; CELL ADHESION; CELL ADHESION MOLECULES; CELL COMMUNICATION; ENDOTHELIAL CELLS; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MUCIN-1; NEOPLASTIC CELLS, CIRCULATING; TRANSENDOTHELIAL AND TRANSEPITHELIAL MIGRATION;

EID: 84862139391     PISSN: 00906964     EISSN: 15739686     Source Type: Journal    
DOI: 10.1007/s10439-011-0463-6     Document Type: Review

References (180)

1. Agastin, S., U. B. T. Giang, Y. Geng, L. A. DeLouise, and M. R. King. Continuously perfused microbubble array for 3D tumor spheroid model. Biomicrofluidics 5(2):24110, 2011.
2. Aigner, S., C. L. Ramos, A. Hafezi-Moghadam, M. B. Lawrence, J. Friederichs, P. Altevogt, and K. Ley. Cd24 mediates rolling of breast carcinoma cells on P-selectin. FASEB J. 12(12):1241-1251, 1998. (Pubitemid 28418954)
3. Aigner, S., Z. M. Sthoeger, M. Fogel, E. Weber, J. Zarn, M. Ruppert, Y. Zeller, D. Vestweber, R. Stahel, M. Sammar, and P. Altevogt. CD24, a mucin-type glyco-protein, is a ligand for P-selectin on human tumor cells. Blood 89(9):3385-3395, 1997. (Pubitemid 27229826)
4. Ajioka, Y., L. J. Allison, and J. R. Jass. Significance of MUC1 and MUC2 mucin expression in colorectal cancer. J. Clin. Pathol. 49(7):560-564, 1996. (Pubitemid 26232730)
5. Albertsson, P. A., U. Nannmark, and B. R. Johansson. Melanoma cell destruction in the microvasculature of perfused hearts is reduced by pretreatment with vitaminE. Clin. Exp. Metastasis 13(4):269-276, 1995.
6. Alon, R., D. A. Hammer, and T. A. Springer. Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature 374(6522):539-542, 1995.
7. Alves, C. S., M. M. Burdick, S. N. Thomas, P. Pawar, and K. Konstantopoulos. The dual role of CD44 as a functional P-selectin ligand and fibrin receptor in colon carcinoma cell adhesion. Am. J. Physiol. Cell Physiol. 294(4):C907-C916, 2008. (Pubitemid 351507918)
8. Alves, C. S., S. Yakovlev, L. Medved, and K. Konstan-topoulos. Biomolecular characterization of CD44-fi-brin(ogen) binding: distinct molecular requirements mediate binding of standard and variant isoforms of CD44 to immobilized fibrin(ogen). J. Biol. Chem. 284(2):1177-1189, 2009.
9. Apweiler, R., H. Hermjakob, and N. Sharon. On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. Biochim. Biophys. Acta 1473(1):4-8, 1999.
10. Becker, D. J., and J. B. Lowe. Fucose: biosynthesis and biological function in mammals. Glycobiology 13(7):41R-53R, 2003. (Pubitemid 36850123)
11. Bell, G. Models for the specific adhesion of cells to cells. Science 200(4342):618-627, 1978.
12. Berg, E. L., L. M. McEvoy, C. Berlin, R. F. Bargatze, and E. C. Butcher. L-selectin-mediated lymphocyte rolling on MADCAM-1. Nature 366(6456):695-698, 1993. (Pubitemid 24036018)
13. Borsig, L., R. Wong, R. O. Hynes, N. M. Varki, and A. Varki. Synergistic effects of L- and P-selectin in facil itating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc. Natl Acad. Sci. USA 99(4):2193-2198, 2002. (Pubitemid 34169037)
14. Brady, J. F., and G. Bossis. Stokesian dynamics. Annu. Rev. Fluid Mech. 20:111-157, 1988.
15. Brayman, M., A. Thathiah, and D. D. Carson. MUC1: a multifunctional cell surface component of reproductive tissue epithelia. Reprod. Biol. Endocrinol. 2:4, 2004.
16. Brockhausen, I. Pathways of O-glycan biosynthesis in cancer cells. Biochim. Biophys. Acta 1473(1):67-95, 1999.
17. Brooks, D. E. The biorheology of tumor-cells. Biorheol-ogy 21(1-2):85-91, 1984.
18. Brooks, S. A., and D. M. S. Hall. Investigations into the potential role of aberrant N-acetylgalactosamine glycans in tumour cell interactions with basement membrane components. Clin. Exp. Metastasis 19(6):487-493, 2002. (Pubitemid 35178666)
19. Buisine, M. P., L. Devisme, P. Degand, M. C. Dieu, B. Gosselin, M. C. Copin, J. P. Aubert, and N. Porchet. Developmental mucin gene expression in the gastroduo- denal tract and accessory digestive glands. II. Duodenum and liver, gallbladder, and pancreas. J. Histochem. Cyto-chem. 48(12):1667-1676, 2000.
20. Burchell, J., S. Gendler, J. Taylorpapadimitriou, A. Girling, A. Lewis, R. Millis, and D. Lamport. Development and characterization of breast-cancer reactive monoclonal-antibodies directed to the core protein of the humanmilk mucin. Cancer Res. 47(20):5476-5482, 1987. (Pubitemid 17152966)
21. Burdick, M. D., A. Harris, C. J. Reid, T. Iwamura, and M. A. Hollingsworth. Oligosaccharides expressed an MUC1 produced by pancreatic and colon tumor cell lines. J. Biol. Chem. 272(39):24198-24202, 1997. (Pubitemid 27418619)
22. Burdick, M. M., J. M. McCaffery, Y. S. Kim, B. S. Bochner, and K. Konstantopoulos. Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECS under flow. Am. J. Physiol. Cell Physiol 284(4):C977-C987, 2003. (Pubitemid 36336954)
23. Butcher, E. C. Leukocyte-endothelial cell recognition: three (or more) steps to specificity and diversity. Cell 67(6):1033-1036, 1991. (Pubitemid 121001517)
24. Caputo, K. E., and D. A. Hammer. Effect of microvillus deformability on leukocyte adhesion explored using adhesive dynamics simulations. Biophys. J. 89(1):187-200, 2005. (Pubitemid 41098275)
25. Carraway, K. L., and S. R. Hull. O-glycosylation pathway for mucin-type glycoproteins. Bioessays 10(4):117-121, 1989.
26. Chang, K. C., D. F. J. Tees, and D. A. Hammer. The state diagram for cell adhesion under flow: Leukocyte rolling and firm adhesion. Proc. Natl Acad. Sci. USA 97(21): 11262-11267, 2000.
27. Chotard-Ghodsnia, R., O. Haddad, A. Leyrat, A. Dro-chon, C. Verdier, and A. Duperray. Morphological analysis of tumor cell/endothelial cell interactions under shear flow. J. Biomech. 40(2):335-344, 2007. (Pubitemid 44958579)
28. Damiano, E. R., J. Westheider, A. Tozeren, and K. Ley. Variation in the velocity, deformation, and adhesion energy density of leukocytes rolling within venules. Circ. Res. 79(6):1122-1130, 1996. (Pubitemid 26404144)
29. de Vries, T., R. M. A. Knegtel, E. H. Holmes, and B. A. Macher. Fucosyltransferases: structure/function studies. Glycobiology 11(10):119R-128R, 2001. (Pubitemid 32982658)
30. Dennis, J. W., M. Granovsky, and C. E. Warren. Gly-coprotein glycosylation and cancer progression. Biochim. Biophys. Acta 1473(1):21-34, 1999.
31. Diamond, M. S., D. E. Staunton, A. R. Defougerolles, S. A. Stacker, J. Garciaaguilar, M. L. Hibbs, and T. A. Springer. ICAM-1 (CD54)-a counter-receptor for mac-1 (CD11b/CD18). J. Cell Biol. 111(6):3129-3139, 1990. (Pubitemid 120034048)
32. Dimitroff, C. J., L. Descheny, N. Trujillo, R. Kim, V. Nguyen, W. Huang, K. J. Pienta, J. L. Kutok, and M. A. Rubin. Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1 and E-selectin ligand-1, on human metastatic prostate tumor cells. Cancer Res. 65(13):5750-5760, 2005. (Pubitemid 40911178)
33. Dimitroff, C. J., J. Y. Lee, S. Rafii, R. C. Fuhlbrigge, and R. Sackstein. CD44 is a major E-selectin ligand on human hematopoietic progenitor cells. J. Cell Biol. 153(6):1277-1286, 2001. (Pubitemid 34289265)
34. Ding, Z. M., J. E. Babensee, S. I. Simon, H. F. Lu, J. L. Perrard, D. C. Bullard, X. Y. Dai, S. K. Bromley, M. L. Dustin, M. L. Entman, C. W. Smith, and C. M. Ballan-tyne. Relative contribution of LFA-1 and MAC-1 to neutrophil adhesion and migration. J. Immunol. 163(9):5029-5038, 1999. (Pubitemid 29501271)
35. Dokurno, P., P. A. Bates, H. A. Band, L. M. D. Stewart, J. M. Lally, J. M. Burchell, J. Taylor-Papadimitriou, D. Snary, M. J. E. Sternberg, and P. S. Freemont. Crystal structure at 1.95 angstrom resolution of the breast tumour-specific antibody SM3 complexed with its peptide epitope reveals novel hypervariable loop recognition. J. Mol. Biol. 284(3):713-728, 1998. (Pubitemid 28550017)
36. Dong, C., J. Cao, E. J. Struble, and H. W. Lipowsky. Mechanics of leukocyte deformation and adhesion to endothelium in shear flow. Ann. Biomed. Eng. 27(3):298-312, 1999. (Pubitemid 129647572)
37. Dong, C., and X. X. Lei. Biomechanics of cell rolling: shear flow, cell-surface adhesion, and cell deformability. J. Biomech. 33(1):35-43, 2000.
38. Dong, C., R. Skalak, K. L. P. Sung, G. W. Schmids-chonbein, and S. Chien. Passive deformation analysis of human-leukocytes. J. Biomech. Eng. 110(1):27-36, 1988.
39. Duncan, T. J., N. F. S. Watson, A. H. Al-Attar, J. H. Scholefield, and L. G. Durrant. The role of muc1 and muc3 in the biology and prognosis of colorectal cancer. World J. Surg. Oncol. 5:31, 2007.
40. Edelman, M. J., P. Potter, K. G. Mahaffey, R. Frink, and R. B. Leidich. The potential for reintroduction of tumor cells during intraoperative blood salvage: reduction of risk with use of the RC-400 leukocyte depletion filter. Urology 47(2):179-181, 1996. (Pubitemid 26075270)
41. Fernandez-Rodriguez, J., O. Dwir, R. Alon, and G. C. Hansson. Tumor cell MUC1 and CD43 are glycosylated differently with sialyl-Lewis a and x epitopes and show variable interactions with E-selectin under physiological flow conditions. Glycoconj. J. 18(11-12):925-930, 2001. (Pubitemid 36315057)
42. Finger, E. B., R. E. Bruehl, D. F. Bainton, and T. A. Springer. A differential role for cell shape in neutrophil tethering and rolling on endothelial selectins under flow. J. Immunol. 157(11):5085-5096, 1996. (Pubitemid 126449590)
43. Friederichs, J., Y. Zeller, A. Hafezi-Moghadam, H. J. Grone, K. Ley, and P. Altevogt. The CD24/P-selectin binding pathway initiates lung arrest of human A125 adenocarcinoma cells. Cancer Res. 60(23):6714-6722, 2000.
44. Fruhauf, N. R., O. Dumpich, C. P. Kaudel, S. KasimirBauer, and K. J. Oldhafer. Filtration of malignant cells: tumour cell depletion in an ex vivo model using a leukocyte adhesion filter. Perfusion 16:51-55, 2001. (Pubitemid 32322012)
45. Fuster, M. M., and J. D. Esko. The sweet and sour of cancer: glycans as novel therapeutic targets. Nat. Rev. Cancer 5(7):526-542, 2005. (Pubitemid 40942829)
46. Gallegos, B., E. Perez-Campos, R. Martinez, P. Leyva, M. Martinez, R. Hernandez, S. Pina, C. Hernandez, E. Zenteno, and P. Hernandez. O-glycosylation expression in fibroadenoma. Prep. Biochem. Biotechnol. 40(1):1-12, 2010.
47. Gay, L. J., and B. Felding-Habermann. Contribution of platelets to tumour metastasis. Nat. Rev. Cancer 11(2):123-134, 2011.
48. Gendler, S. J. MUC1, the renaissance molecule. J. Mammary Gland Biol. Neoplasia 6(3):339-353, 2001.
49. Geng, Y., S. Narasipura, G. M. Seigel, and M. R. King. Vascular recruitment of human retinoblastoma cells by multi-cellular adhesive interactions with circulating leukocytes. Cell. Mol. Bioeng. 3(4):361-368, 2010.
50. Girling, A., J. Bartkova, J. Burchell, S. Gendler, C. Gil-lett, and J. Taylorpapadimitriou. A core protein epitope of the polymorphic epithelial mucin detected by the monoclonal-antibody SM-3 is selectively exposed in a range of primary carcinomas. Int. J. Cancer 43(6):1072-1076, 1989. (Pubitemid 19158040)
51. Goetz, D. J., D. A. Hammer, and B. U. Pauli. LU-ECAM-1-mediated adhesion of melanoma cells to endo-thelium under conditions of flow. Int. J. Cancer 65(2):192-199, 1996. (Pubitemid 26051682)
52. Goswami, K., H. Nandeesha, B. Koner, and D. Nan-dakumar. A comparative study of serum protein-bound sialic acid in benign and malignant prostatic growth: possible role of oxidative stress in sialic acid homeostasis. Prostate Cancer and Prostatic Dis. 10(4):356-359, 2007. (Pubitemid 350238084)
53. Guddo, F., A. Giatromanolaki, M. I. Koukourakis, A. M. Vignola, G. Chlouverakis, J. Hilkens, K. C. Gatter, A. L. Harris, and G. Bonsignore. MUC1 (episialin) expression in non-small cell lung cancer is independent of EGFR and c-erbB-2 expression and correlates with poor survival in node positive patients. J. Clin. Pathol. 51(9):667-671, 1998. (Pubitemid 28423725)
54. Hammer, D. A. Leukocyte adhesion: what's the catch? Curr. Biol. 15(3):R96-R99, 2005. (Pubitemid 40205696)
55. Hammer, D. A., and S. M. Apte. Simulation of cell rolling and adhesion on surfaces in shear-flow-general results and analysis of selectin-mediated neutrophil adhesion. Biophys. J. 63(1):35-57, 1992.
56. Hanisch, F. A. O-glycosylation of the mucin type. Biol. Chem. 382(2):143-149, 2001.
57. Hanley, W. D., M. M. Burdick, K. Konstantopoulos, and R. Sackstein. CD44 on LS174T colon carcinoma cells possesses E-selectin ligand activity. Cancer Res. 65(13):5812-5817, 2005. (Pubitemid 40911185)
58. Hanley, W. D., S. L. Napier, M. M. Burdick, R. L. Schnaar, R. Sackstein, and K. Konstantopoulos. Variant isoforms of CD44 are P- and L-selectin ligands on colon carcinoma cells. FASEB J. 19(14):337-339, 2005.
59. Hentzen, E. R., S. Neelamegham, G. S. Kansas, J. A. Benanti, L. V. McIntire, C. W. Smith, and S. I. Simon. Sequential binding of CD11a/CD18 and CD11b/CD18 defines neutrophil capture and stable adhesion to intercellular adhesion molecule-1. Blood 95(3):911-920, 2000. (Pubitemid 30062713)
60. Hollingsworth, M. A., and B. J. Swanson. Mucins in cancer: protection and control of the cell surface. Nat. Rev. Cancer 4(1):45-60, 2004. (Pubitemid 38082153)
61. Huang, Z., and M. R. King. An immobilized nanoparti-cle-based platform for efficient gene knockdown of targeted cells in the circulation. Gene Ther. 16(10):1271-1282, 2009.
62. Inata, J., N. Hattori, A. Yokoyama, S. Ohshimo, M. Doi, N. Ishikawa, H. Hamada, and N. Kohno. Circulating KL-6/MUC1 mucin carrying sialyl Lewis(a) oligosaccha-ride is an independent prognostic factor in patients with lung adenocarcinoma. Int. J. Cancer 120(12):2643-2649, 2007. (Pubitemid 46651286)
63. Jadhav, S., B. S. Bochner, and K. Konstantopoulos. Hydrodynamic shear regulates the kinetics and receptor specificity of polymorphonuclear leukocyte-colon carcinoma cell adhesive interactions. J. Immunol. 167(10):5986-5993, 2001. (Pubitemid 33062796)
64. Jadhav, S., C. D. Eggleton, and K. Konstantopoulos. A 3-D computational model predicts that cell deformation affects selectin-mediated leukocyte rolling. Biophys. J. 88(1):96-104, 2005. (Pubitemid 40070661)
65. Jadhav, S., and K. Konstantopoulos. Fluid shear- and time-dependent modulation of molecular interactions between PMNS and colon carcinomas. Am. J. Physiol. Cell Physiol. 283(4):C1133-C1143, 2002.
66. Jin, Q., C. Verdier, P. Singh, N. Aubry, R. Chotard-Ghodsnia, and A. Duperray. Migration and deformation of leukocytes in pressure driven flows. Mech. Res. Commun. 34(5-6):411-422, 2007. (Pubitemid 47284406)
67. Johnson, F. E., M. Zhou, B. T. Collins, and J. S. Huang. Mechanical deformation induces proliferation of human colorectal carcinoma cells. Int. J. Oncol. 16(3):617-622, 2000.
68. Kansas, G. S. Selectins and their ligands: current concepts and controversies. Blood 88(9):3259-3287, 1996. (Pubitemid 26365560)
69. Kelly, C. P., J. C. Okeane, J. Orellana, P. C. Schroy, S. Yang, J. T. Lamont, and H. R. Brady. Human colon cancer-cells express ICAM-1 invivo and support LFA-1-dependent lymphocyte adhesion invitro. Am. J. Physiol. 263(6):G864-G870, 1992. (Pubitemid 23033273)
70. Khismatullin, D. B., and G. A. Truskey. A 3D numerical study of the effect of channel height on leukocyte deformation and adhesion in parallel-plate flow chambers. Microvasc. Res. 68(3):188-202, 2004.
71. Kim, Y. J., L. Borsig, H. L. Han, N. M. Varki, and A. Varki. Distinct selectin ligands on colon carcinoma muc-ins can mediate pathological interactions among platelets, leukocytes, and endothelium. Am. J. Pathol. 155(2):461-472, 1999. (Pubitemid 29370396)
72. Kim, Y. J., L. Borsig, N. M. Varki, and A. Varki. P-selectin deficiency attenuates tumor growth and metastasis. Proc. Natl Acad. Sci. USA 95(16):9325-9330, 1998. (Pubitemid 28506230)
73. Kim, Y. S., J. Gum, and I. Brockhausen. Mucin glyco-proteins in neoplasia. Glycoconj. J. 13(5):693-707, 1996.
74. King, M. R., D. Bansal, M. B. Kim, and I. H. Sarelius. The effect of hematocrit and leukocyte adherence on flow direction in the microcirculation. Ann. Biomed. Eng. 32(6):803-814, 2004.
75. King, M. R., and D. A. Hammer. Multiparticle adhesive dynamics: hydrodynamic recruitment of rolling leukocytes. Proc. Natl Acad. Sci. USA 98(26):14919-14924, 2001. (Pubitemid 34013945)
76. King, M. R., and D. A. Hammer. Multiparticle adhesive dynamics. Interactions between stably rolling cells. Bio-phys. J. 81(2):799-813, 2001. (Pubitemid 32721453)
77. King, M. R., V. Heinrich, E. Evans, and D. A. Hammer. Nano-to-micro scale dynamics of P-selectin detachment from leukocyte interfaces. III. Numerical simulation of tethering under flow. Biophys. J. 88(3):1676-1683, 2005. (Pubitemid 40976184)
78. King, M. R., M. B. Kim, I. H. Sarelius, and D. A. Hammer. Hydrodynamic interactions between rolling leukocytes in vivo. Microcirculation 10(5):401-409, 2003. (Pubitemid 39004266)
79. King, M. R., S. D. Rodgers, and D. A. Hammer. Hydrodynamic collisions suppress fluctuations in the rolling velocity of adhesive blood cells. Langmuir 17(14):4139-4143, 2001. (Pubitemid 35330277)
80. King, M. R., A. D. Ruscio, M. B. Kim, and I. H. Sarelius. Interactions between stably rolling leukocytes in vivo. Phys. Fluids 17(3):031501, 2005.
81. King, M. R., R. Sumagin, C. E. Green, and S. I. Simon. Rolling dynamics of a neutrophil with redistributed L-selectin. Math. Biosci. 194(1):71-79, 2005. (Pubitemid 40523790)
82. King, M. R., L. T. Western, K. Rana, and J. L. Liesveld. Biomolecular surfaces for the capture and reprogramming of circulating tumor cells. J. Bionic Eng. 6(4):311-317, 2009.
83. Kocer, B., A. Soran, G. Kiyak, S. Erdogan, A. Eroglu, B. Bozkurt, C. Solak, and O. Cengiz. Prognostic significance of mucin expression in gastric carcinoma. Dig. Dis. Sci. 49(6):954-964, 2004. (Pubitemid 39012278)
84. Kohler, S., S. Ullrich, U. Richter, and U. Schumacher. E-/P-selectins and colon carcinoma metastasis: first in vivo evidence for their crucial role in a clinically relevant model of spontaneous metastasis formation in the lung. Br. J. Cancer 102(3):602-609, 2010.
85. Konstantopoulos, K., and S. N. Thomas. Cancer cells in transit: the vascular interactions of tumor cells. Annu. Rev. Biomed. Eng. 11:177-202, 2009.
86. Korn, C. B., and U. S. Schwarz. Dynamic states of cells adhering in shear flow: from slipping to rolling. Phys. Rev. E 77(4):041904, 2008.
87. Krasik, E. F., K. E. Caputo, and D. A. Hammer. Adhesive dynamics simulation of neutrophil arrest with stochastic activation. Biophys. J. 95(4):1716-1728, 2008.
88. Lawrence, M. B., and T. A. Springer. Leukocytes roll on a selectin at physiological flow-rates-distinction from and prerequisite for adhesion through integrins. Cell 65(5):859-873, 1991. (Pubitemid 121001317)
89. Lawrence, M. B., and T. A. Springer. Neutrophils roll on E-selectin. J. Immunol. 151(11):6338-6346, 1993. (Pubitemid 23340380)
90. Lee, D., K. E. Caputo, D. A. Hammer, and M. R. King. Adhesive dynamics simulations of the mechanical shedding of L-selectin from the neutrophil surface. J. Theor. Biol. 260(1):27-30, 2009.
91. Lee, D., and M. R. King. Shear-induced capping of L-selectin on the neutrophil surface during centrifugation. J. Immunol. Methods 328(1-2):97-105, 2007. (Pubitemid 350007622)
92. Lee, M. J., H. S. Lee, W. H. Kim, Y. Choi, and M. H. Yang. Expression of mucins and cytokeratins in primary carcinomas of the digestive system. Mod. Pathol. 16(5):403-410, 2003. (Pubitemid 36618459)
93. Lee, D., J. B. Schultz, P. A. Knauf, and M. R. King. Mechanical shedding of L-selectin from the neutrophil surface during rolling on sialyl Lewis x under flow. J. Biol. Chem. 282(7):4812-4820, 2007. (Pubitemid 47100965)
94. Ley, K., C. Laudanna, M. I. Cybulsky, and S. Nour-shargh. Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat. Rev. Immunol. 7(9):678-689, 2007. (Pubitemid 47327397)
95. Liang, S., M. Hoskins, P. Khanna, R. F. Kunz, and C. Dong. Effects of the tumor-leukocyte microenvironment on melanoma-neutrophil adhesion to the endothelium in a shear flow. Cell. Mol. Bioeng. 1(2-3):189-200, 2008.
96. Liang, L., L. Qu, and Y. Ding. Protein and mRNA characterization in human colorectal carcinoma cell lines with different metastatic potentials. Cancer Invest. 25(6):427-434, 2007. (Pubitemid 47450672)
97. Liang, S., M. J. Slattery, D. Wagner, S. I. Simon, and C. Dong. Hydrodynamic shear rate regulates melanoma-leukocyte aggregation, melanoma adhesion to the endo-thelium, and subsequent extravasation. Ann. Biomed. Eng. 36(4):661-671, 2008.
98. Lichtenstein, A. Stimulation of the respiratory burst of murine peritoneal inflammatory neutrophils by conjugation with tumor-cells. Cancer Res. 47(9):2211-2217, 1987. (Pubitemid 17099173)
99. Lloyd, K. O., J. Burchell, V. Kudryashov, B. W. T. Yin, and J. Taylor-Papadimitriou. Comparison of O-linked carbohydrate chains in MUC-1 mucin from normal breast epithelial cell lines and breast carcinoma cell lines-demonstration of simpler and fewer glycan chains in tumor cells. J. Biol. Chem. 271(52):33325-33334, 1996. (Pubitemid 27010142)
100. Lou, J. Z., T. Yago, A. G. Klopocki, P. Mehta, W. Chen, V. I. Zarnitsyna, N. V. Bovin, C. Zhu, and R. P. McEver. Flow-enhanced adhesion regulated by a selectin interdomain hinge. J. Cell Biol. 174(7):1107-1117, 2006. (Pubitemid 44455197)
101. Lowe, J. B. Glycosylation in the control of selectin counter-receptor structure and function. Immunol. Rev. 186:19-36, 2002.
102. Lu, J. G., Y. Li, L. Li, and X. Kan. Overexpression of osteopontin and integrin av in laryngeal and hypopha-ryngeal carcinomas associated with differentiation and metastasis. J. Cancer Res. Clin. Oncol. 137(11):1613-1618, 2011.
103. Ma, B., J. L. Simala-Grant, and D. E. Taylor. Fucosyla-tion in prokaryotes and eukaryotes. Glycobiology 16(12):158R-184R, 2006.
104. MacLean, G. D., M. A. Reddish, and B. M. Longenecker. Prognostic significance of preimmunotherapy serum CA27.29 (MUC-1) mucin level after active specific immunotherapy of metastatic adenocarcinoma patients. J. Immunother. 20(1):70-78, 1997. (Pubitemid 28011526)
105. Maruo, Y., A. Gochi, A. Kaihara, H. Shimamura, T. Yamada, N. Tanaka, and K. Orita. ICAM-1 expression and the soluble ICAM-1 level for evaluating the metastatic potential of gastric cancer. Int. J. Cancer 100(4):486-490, 2002.
106. Masaki, Y., M. Oka, Y. Ogura, T. Ueno, K. Nishihara, A. Tangoku, M. Takahashi, M. Yamamoto, and T. Irimura. Sialylated MUC1 mucin expression in normal pancreas, benign pancreatic lesions, and pancreatic ductal adenocar-cinoma. Hepato-Gastroenterology 46(28):2240-2245, 1999. (Pubitemid 29454075)
107. McEver, R. P. Selectins: lectins that initiate cell adhesion under flow. Curr. Opin. Cell Biol. 14(5):581-586, 2002. (Pubitemid 35247741)
108. McIntyre, T. M., S. M. Prescott, A. S. Weyrich, and G. A. Zimmerman. Cell-cell interactions: leukocyte-endothelial interactions. Curr. Opin. Hematol. 10(2):150-158, 2003. (Pubitemid 36207971)
109. Minner, S., F. Kraetzig, M. Tachezy, E. Kilic, M. Grae-fen, W. Wilczak, C. Bokemeyer, H. Huland, G. Sauter, and T. Schlomm. Low activated leukocyte cell adhesion molecule expression is associated with advanced tumor stage and early prostate-specific antigen relapse in prostate cancer. Hum. Pathol. 42(12):1946-1952, 2011.
110. Mong, T. K. K., H. K. Lee, S. G. Duron, and C. H. Wong. Reactivity-based one-pot total synthesis of fucose GM(1) oligosaccharide: a sialylated antigenic epitope of small-cell lung cancer. Proc. Natl Acad. Sci. USA 100(3):797-802, 2003. (Pubitemid 36183910)
111. Moniaux, N., F. Escande, N. Porchet, J. P. Aubert, and S. K. Batra. Structural organization and classification of the human mucin genes. Front. Biosci. 6:D1192-D1206, 2001.
112. Monzavi-Karbassi, B., J. S. Stanley, L. Hennings, F. Jousheghany, C. Artaud, S. Shaaf, and T. Kieber-Em-mons. Chondroitin sulfate glycosaminoglycans as major P-selectin ligands on metastatic breast cancer cell lines. Int. J. Cancer 120(6):1179-1191, 2007.
113. Moore, K. L., S. F. Eaton, D. E. Lyons, H. S. Lichenstein, R. D. Cummings, and R. P. McEver. The P-selectin gly-coprotein ligand from human neutrophils displays sialy-lated, fucosylated, O-linked poly-N- acetyllactosamine. J. Biol. Chem. 269(37):23318-23327, 1994. (Pubitemid 24283324)
114. Moss, M. A., and K. W. Anderson. Adhesion of cancer cells to endothelial monolayers: a study of initial attachment versus firm adhesion. J. Adhes. 74(1-4):19-40, 2000. (Pubitemid 32514038)
115. Myung, J. H., K. A. Gajjar, R. M. Pearson, C. A. Launiere, D. T. Eddington, and S. Hong. Direct measurements on CD24-mediated rolling of human breast cancer MCF-7 cells on E-selectin. Anal. Chem. 83(3):1078-1083, 2011.
116. Nagrath, S., L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digu-marthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber, and M. Toner. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235-1239, 2007.
117. Narasipura, S. D., J. C. Wojciechowski, B. M. Duffy, J. L. Liesveld, and M. R. King. Purification of CD45+ hema-topoietic cells directly from human bone marrow using a flow-based P-selectin-coated microtube. Am. J. Hematol. 83(8):627-629, 2008.
118. Norgard, K. E., K. L. Moore, S. Diaz, N. L. Stults, S. Ushiyama, R. P. McEver, R. D. Cummings, and A. Varki. Characterization of a specific ligand for P-selectin on myeloid cells-a minor glycoprotein with sialylated O-linked oligosaccharides. J. Biol. Chem. 268(17):12764-12774, 1993. (Pubitemid 23182445)
119. Ohtsubo, K., and J. D. Marth. Glycosylation in cellular mechanisms of health and disease. Cell 126(5):855-867, 2006. (Pubitemid 44310784)
120. Orr, F. W., H. H. Wang, R. M. Lafrenie, S. Scherbarth, and D. M. Nance. Interactions between cancer cells and the endothelium in metastasis. J. Pathol. 190(3):310-329, 2000. (Pubitemid 30141377)
121. Park, E. Y. H., M. J. Smith, E. S. Stropp, K. R. Snapp, J. A. DiVietro, W. F. Walker, D. W. Schmidtke, S. L. Diamond, and M. B. Lawrence. Comparison of PSGL-1 mi-crobead and neutrophil rolling: microvillus elongation stabilizes P-selectin bond clusters. Biophys. J. 82(4):1835-1847, 2002. (Pubitemid 34280800)
122. Patsos, G., V. Hebbe-Viton, C. Robbe-Masselot, D. Masselot, R. S. Martin, R. Greenwood, C. Paraskeva, A. Klein, M. Graessmann, J. C. Michalski, T. Gallagher, and A. Corfield. O-glycan inhibitors generate aryl-glycans, induce apoptosis and lead to growth inhibition in colo-rectal cancer cell lines. Glycobiology 19(4):382-398, 2009.
123. Perseghin, P., M. Vigano, G. Rocco, C. DellaPona, A. Buscemi, and A. Rizzi. Effectiveness of leukocyte filters in reducing tumor cell contamination after intraoperative blood salvage in lung cancer patients. Vox Sang. 72(4):221-224, 1997. (Pubitemid 27277714)
124. Phan, U. T., T. T. Waldron, and T. A. Springer. Remodeling of the lectin-EGF-like domain interface in P- and L-selectin increases adhesiveness and shear resistance under hydrodynamic force. Nat. Immunol. 7(8):883-889, 2006. (Pubitemid 44084096)
125. Pouyani, T., and B. Seed. PSGL-1 recognition of P-selectin is controlled by a tyrosine sulfation consensus at the PSGL-1 amino-terminus. Cell 83(2):333-343, 1995.
126. Puri, K. D., E. B. Finger, G. Gaudernack, and T. A. Springer. Sialomucin CD34 is the major L-selectin ligand in human tonsil high endothelial venules. J. Cell Biol. 131(1):261-270, 1995.
127. Qi, Y. J., Q. Y. He, Y. F. Ma, Y. W. Du, G. C. Liu, Y. J. Li, G. S. Tsao, S. M. Ngai, and J. F. Chiu. Proteomic identification of malignant transformation-related proteins in esophageal squamous cell carcinoma. J. Cell. Biochem. 104(5):1625-1635, 2008.
128. Queen, M. M., R. E. Ryan, R. G. Holzer, C. R. KellerPeck, and C. L. Jorcyk. Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression. Cancer Res. 65(19):8896-8904, 2005. (Pubitemid 41377379)
129. Rachagani, S., M. P. Torres, N. Moniaux, and S. K. Ba-tra. Current status of mucins in the diagnosis and therapy of cancer. Biofactors 35(6):509-527, 2009.
130. Rahn, J., J. Chow, G. Horne, B. Mah, J. Emerman, P. Hoffman, and J. Hugh. MUC1 mediates transendothelial migration in vitro by ligating endothelial cell ICAM-1. Clin Exp. Metastasis 6:475-483, 2005. (Pubitemid 41750699)
131. Raman, P. S., C. S. Alves, D. Wirtz, and K. Konstanto-poulos. Single-molecule binding of CD44 to fibrin versus P-selectin predicts their distinct shear-dependent interactions in cancer. J. Cell Sci. 124(11):1903-1910, 2011.
132. Rana, K., J. L. Liesveld, and M. R. King. Delivery of apoptotic signal to rolling cancer cells: a novel biomimetic technique using immobilized trail and E-selectin. Bio-technol. Bioeng. 102(6):1692-1702, 2009.
133. Reis, C. A., H. Osorio, L. Silva, C. Gomes, and L. David. Alterations in glycosylation as biomarkers for cancer detection. J. Clin. Pathol. 63(4):322-329, 2010.
134. Retz, M., J. Lehmann, C. Roder, B. Plotz, J. Harder, J. Eggers, J. Pauluschke, H. Kalthoff, and M. Stockle. Differential mucin MUC7 gene expression in invasive bladder carcinoma in contrast to uniform MUC1 and MUC2 gene expression in both normal urothelium and bladder carcinoma. Cancer Res. 58(24):5662-5666, 1998. (Pubitemid 29006401)
135. Riethdorf, S., H. Fritsche, V. Muller, T. Rau, C. Schindibeck, B. Rack, W. Janni, C. Coith, K. Beck, F. Janicke, S. Jackson, T. Gornet, M. Cristofanilli, and K. Pantel. Detection of circulating tumor cells in peripheral blood of patients with metastatic breast cancer: A validation study of the cell search system. Clin. Cancer Res. 13(3):920-928, 2007. (Pubitemid 46340368)
136. Ringel, J., and M. Lohr. The MUC gene family: their role in diagnosis and early detection of pancreatic cancer. Mol. Cancer 2:9, 2003.
137. Rosette, C., R. B. Roth, P. Oeth, A. Braun, S. Kammerer, J. Ekblom, and M. F. Denissenko. Role of ICAM1 in invasion of human breast cancer cells. Carcinogenesis 26(5):943-950, 2005. (Pubitemid 41214323)
138. Schaff, U., P. E. Mattila, S. I. Simon, and B. Walcheck. Neutrophil adhesion to E-selectin under shear promotes the redistribution and co-clustering of ADAM17 and its proteolytic substrate L-selectin. J. Leukoc. Biol. 83(1):99-105, 2008.
139. Schmidtke, D. W., and S. L. Diamond. Direct observation of membrane tethers formed during neutrophil attachment to platelets or P-selectin under physiological flow. J. Cell Biol. 149(3):719-729, 2000. (Pubitemid 30252404)
140. Shao, J. Y., H. P. Ting-Beall, and R. M. Hochmuth. Static and dynamic lengths of neutrophil microvilli. Proc. Natl Acad. Sci. USA 95(12):6797-6802, 1998. (Pubitemid 28278060)
141. Shimodaira, K., J. Nakayama, N. Nakamura, O. Hasebe, T. Katsuyama, and M. Fukuda. Carcinoma-associated expression of core 2 beta-1, 6-N- acetylglucosaminyl-transferase gene in human colorectal cancer: role of O-glycans in tumor progression. Cancer Res. 57(23):5201-5206, 1997. (Pubitemid 27516348)
142. Shirure, V. S., K. A. Henson, R. L. Schnaar, L. Nim-richter, and M. M. Burdick. Gangliosides expressed on breast cancer cells are E-selectin ligands. Biochem. Bio-phys. Res. Commun. 406(3):423-429, 2011.
143. Sihto, H., J. Lundin, M. Lundin, T. Lehtimaki, A. Risti-maki, K. Holli, L. Sailas, V. Kataja, T. Turpeenniemi-Hujanen, J. Isola, P. Heikkila, and H. Joensuu. Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study. Breast Cancer Res. 13(5):R87, 2011.
144. Slattery, M. J., and C. Dong. Neutrophils influence melanoma adhesion and migration under flow conditions. Int. J. Cancer 106(5):713-722, 2003. (Pubitemid 36993395)
145. Smith, C. W. Possible steps involved in the transition to stationary adhesion of rolling neutrophils: a brief review. Microcirculation 7(6):385-394, 2000.
146. Smith, M. J., E. L. Berg, and M. B. Lawrence. A direct comparison of selectin-mediated transient, adhesive events using high temporal resolution. Biophys. J. 77(6):3371-3383, 1999.
147. Springer, T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76(2):301-314, 1994. (Pubitemid 24046692)
148. Springer, T. A. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu. Rev. Physiol. 57:827-872, 1995.
149. Steeber, D. A., and T. F. Tedder. Adhesion molecule cascades direct lymphocyte recirculation and leukocyte migration during inflammation. Immunol. Res. 22(2-3):299-317, 2000. (Pubitemid 32382242)
150. Steegmaier, M., J. E. Blanks, E. Borges, and D. Vestwe-ber. P-selectin glycoprotein ligand-1 mediates rolling of mouse bone marrow-derived mast cells on P-selectin but not efficiently on E-selectin. Eur. J. Immunol. 27(6):1339-1345, 1997. (Pubitemid 27254822)
151. Steegmaier, M., A. Levinovitz, S. Isenmann, E. Borges, M. Lenter, H. P. Kocher, B. Kleuser, and D. Vestweber. The E-selectin-ligand ESL-1 is a variant
152. Taylor-Papadimitriou, J., J. M. Burchell, T. Plunkett, R. Graham, I. Correa, D. Miles, and M. Smith. MUC1 and the immunobiology of cancer. J. Mammary Gland Biol. Neoplasia 7(2):209-221, 2002. (Pubitemid 38425494)
153. Terada, T., T. Ohta, M. Sasaki, Y. Nakanuma, and Y. S. Kim. Expression of MUC apomucins in normal pancreas and pancreatic tumours. J. Pathol. 180(2):160-165, 1996. (Pubitemid 26370181)
154. Tewes, M., B. Aktas, A. Welt, S. Mueller, S. Hauch, R. Kimmig, and S. Kasimir-Bauer. Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies. Breast Cancer Res. Treat. 115(3):581-590, 2009.
155. Thomas, S. N., R. L. Schnaar, and K. Konstantopoulos. Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells. Am. J. Physiol. Cell Physiol. 296(3):C505-C513, 2009.
156. Thomas, S. N., F. Zhu, R. L. Schnaar, C. S. Alves, and K. Konstantopoulos. Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow. J. Biol. Chem. 283(23):15647-15655, 2008.
157. Tomlinson, J., J. L. Wang, S. H. Barsky, M. C. Lee, J. Bischoff, and M. Nguyen. Human colon cancer cells express multiple glycoprotein ligands for E-selectin. Int. J. Oncol. 16(2):347-353, 2000.
158. Urzua, U., L. Best, and D. J. Munroe. Microarray pro-teomic analysis discriminates tumorigenic mouse ovarian surface epithelial cells of divergent aggressive potential. Mol. Biosyst. 6(12):2521-2528, 2010.
159. Varki, A. Selectin ligands: will the real ones please stand up? J. Clin. Invest. 100(11):S31-S35, 1997. (Pubitemid 28009543)
160. Varki, A. Essentials of Glycobiology. Plainview, NY: Cold Spring Harbor Laboratory Press, 653 pp, 1999.
161. Varki, N. M., and A. Varki. Diversity in cell surface sialic acid presentations: implications for biology and disease. Lab. Invest. 87(9):851-857, 2007. (Pubitemid 47267816)
162. Verdier, C., C. Couzon, A. Duperray, and P. Singh. Modeling cell interactions under flow. J. Math. Biol. 58(1-2):235-259, 2009.
163. Vestweber, D., and J. E. Blanks. Mechanisms that regulate the function of the selectins and their ligands. Physiol. Rev. 79(1):181-213, 1999. (Pubitemid 29056952)
164. Walcheck, B., K. L. Moore, R. P. McEver, and T. K. Kishimoto. Neutrophil-neutrophil interactions under hydrodynamic shear stress involve L-selectin and PSGL-1-a mechanism that amplifies initial leukocyte accumulation on P-selectin in vitro. J. Clin. Invest. 98(5):1081-1087, 1996. (Pubitemid 26299918)
165. Wang, X., A. A. Shah, R. B. Campbell, and K. T. Wan. Glycoprotein mucin molecular brush on cancer cell surface acting as mechanical barrier against drug delivery. Appl. Phys. Lett. 97(26):263703, 2010.
166. Wilkins, P. P., K. L. Moore, R. P. McEver, and R. D. Cummings. Tyrosine sulfation of P-selectin glycoprotein ligand-1 is required for high-affinity binding to P-selectin. J. Biol. Chem. 270(39):22677-22680, 1995.
167. Wirtz, D., K. Konstantopoulos, and P. C. Searson. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat. Rev. Cancer 11(7):512-522, 2011.
168. Wittekind, C., and M. Neid. Cancer invasion and metastasis. Oncology 69:14-16, 2005. (Pubitemid 41433536)
169. Wojciechowski, J. C., S. D. Narasipura, N. Charles, D. Mickelsen, K. Rana, M. L. Blair, and M. R. King. Capture and enrichment of CD34-positive haematopoietic stem and progenitor cells from blood circulation using P-selectin in an implantable device. Br. J. Haematol. 140(6):673-681, 2008. (Pubitemid 351300916)
170. Wood, S. M., J. Marshall, C. Abram, and M. M. Burdick. Sialofucosylated glycosphingolipids expressed on head and neck cancer cells mediate adhesion to endothelial cells. In: Proceedings of the American Association for Cancer Research Annual Meeting, Vol. 51, p. 1257, 2010.
171. Wood, S. M., J. R. Marshall, C. E. Abram, L. Nimrichter, and M. M. Burdick. Glycosphingolipids are the major E-selectin ligands expressed on head and neck cancer cells. In: Proceedings of the American Association for Cancer Research Annual Meeting, Vol. 50, p. 528, 2009.
172. Yago, T., J. H. Wu, C. D. Wey, A. G. Klopocki, C. Zhu, and R. P. McEver. Catch bonds govern adhesion through L-selectin at threshold shear. J. Cell Biol. 166(6):913-923, 2004. (Pubitemid 39249841)
173. Yamanaka, T., S. Matsumoto, S. Teramukai, R. Ishiwata, Y. Nagai, and M. Fukushima. The baseline ratio of neu-trophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology 73(3-4):215-220, 2007. (Pubitemid 351630053)
174. Yin, L., Y. Q. Li, J. Ren, H. Kuwahara, and D. Kufe. Human MUC1 carcinoma antigen regulates intracel-lular oxidant levels and the apoptotic response to oxidative stress. J. Biol. Chem. 278(37):35458-35464, 2003. (Pubitemid 37102316)
175. Yin, X. Y., K. Rana, V. Ponmudi, and M. R. King. Knockdown of fucosyltransferase III disrupts the adhesion of circulating cancer cells to E-selectin without affecting hematopoietic cell adhesion. Carbohydr. Res. 345(16):2334-2342, 2010.
176. Ying-Tao, Z., G. Yi-Ping, S. Lu-Sheng, and W. Yi-Li. Proteomic analysis of differentially expressed proteins between metastatic and non-metastatic human colorectal carcinoma cell lines. Eur. J. Gastroenterol. Hepatol. 17(7):725-732, 2005.
177. Zhang, K., D. Baeckstrom, H. Brevinge, and G. C. Hansson. Secreted MUC1 mucins lacking their cyto-plasmic part and carrying sialyl-Lewis a and x epitopes from a tumor cell line and sera of colon carcinoma patients can inhibit HL-60 leukocyte adhesion to E-selectin-expressing endothelial cells. J. Cell. Biochem. 60(4):538-549, 1996. (Pubitemid 26112066)
178. Zhang, K., D. Baeckstrom, H. Brevinge, and G. C. Hansson. Comparison of sialyl-Lewis a carrying CD43 and MUC1 mucins secreted from a colon carcinoma cell line for E-selectin binding and inhibition of leukocyte adhesion. Tumor Biol. 18(3):175-187, 1997. (Pubitemid 27204764)
179. Zhang, P., T. Ozdemir, C. Y. Chung, G. P. Robertson, and C. Dong. Sequential binding of avb3 and ICAM-1 determines fibrin-mediated melanoma capture and stable adhesion to CD11b/CD18 on neutrophils. J. Immunol. 186(1):242-254, 2011.
180. Zotter, S., A. Lossnitzer, P. C. Hageman, J. F. M. Delemarre, J. Hilkens, and J. Hilgers. Immunohistochemical localization of the epithelial marker MAM-6 in invasive malignancies and highly dysplastic adenomas of the large-intestine. Lab. Invest. 57(2):193-199, 1987. (Pubitemid 17138775)