Osteopontin: Its potential role in cancer of children and young adults

Biomarkers in Medicine

Volumn 11, Issue 4, 2017, Pages 389-402

  Karpinsky, Gabrielle ^a   Fatyga, Aleksandra ^b   Krawczyk, Malgorzata Anna ^c   Chamera, Madeleine ^d   Sande, Natalia ^d   Szmyd, Dagmara ^e   Izycka Swieszewska, Ewa ^d   Bien, Ewa ^c  

^a CHILDREN'S HOSPITAL OF MICHIGAN   (United States)

^b University Clinical Centre   (Poland)

^c UNIVERSITY OF GDA SK   (Poland)

^d MEDICAL UNIVERSITY OF GDANSK   (Poland)

^e WEST CUMBERLAND HOSPITAL   (United Kingdom)

Author keywords

Brain tumors; Childhood cancers; Langerhans cell histiocytosis; Leukemia; Lymphoma; Osteopontin; Osteosarcoma; Prognostic marker; Sialoprotein 1; SPP1 gene

Indexed keywords

MESSENGER RNA; OSTEOPONTIN; SPP1 PROTEIN, HUMAN; TUMOR MARKER;

ACUTE LYMPHOBLASTIC LEUKEMIA; ADULT; ATYPICAL TERATOID RHABDOID TUMOR; CANCER GROWTH; CANCER PROGNOSIS; CANCER SURVIVAL; CARCINOGENESIS; CENTRAL NERVOUS SYSTEM METASTASIS; CENTRAL NERVOUS SYSTEM TUMOR; CHILD; CHILDHOOD CANCER; DISEASE ASSOCIATION; GENE EXPRESSION; HEMATOPOIETIC STEM CELL; HUMAN; KIDNEY TUMOR; LANGERHANS CELL HISTIOCYTOSIS; LYMPHOMA; LYMPHOPROLIFERATIVE DISEASE; MALIGNANT NEOPLASM; MEDULLOBLASTOMA; OSTEOSARCOMA; PROTEIN ANALYSIS; PROTEIN BLOOD LEVEL; PROTEIN CEREBROSPINAL FLUID LEVEL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SPP1 GENE; STEM CELL NICHE; TREATMENT RESPONSE; YOUNG ADULT; BRAIN NEOPLASMS; CENTRAL NERVOUS SYSTEM NEOPLASMS; GENETICS; LEUKEMIA; METABOLISM; MORTALITY; NEOPLASMS; PATHOLOGY; SURVIVAL RATE;

BIOMARKERS, TUMOR; BRAIN NEOPLASMS; CENTRAL NERVOUS SYSTEM NEOPLASMS; CHILD; HUMANS; LEUKEMIA; NEOPLASMS; OSTEOPONTIN; SURVIVAL RATE; YOUNG ADULT;

EID: 85016769295     PISSN: 17520363     EISSN: 17520371     Source Type: Journal    
DOI: 10.2217/bmm-2016-0308     Document Type: Review

References (116)

1. Reinholt FP, Hultenby K, Oldberg A, Heinegård D. Osteopontin-a possible anchor of osteoclasts to bone. Proc. Natl Acad. Sci. USA 87(12), 4473-4475 (1990).
2. Franzén A, Heinegård D. Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem. J. 232(3), 715-724 (1985).
3. Prince CW, Butler WT. 1, 25-Dihydroxyvitamin D3 regulates the biosyntheis of osteopontin, a bone-derived cell attachment protein, in clonal osteoblast0like osteosarcoma cells. Coll. Relat. Res. 7(4), 305-313 (1987).
4. Senger DR, Perruzzi CA, Papadopoulos A. Elevated expression of secreted phosphoprotein I (osteopontin, 2ar) as a consequence of neoplastic transformation. Anticancer Res. 9(5), 1291-1299 (1989).
5. Patarca R, Freeman GJ, Singh RP, et al. Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection. J. Exp. Med. 170(1), 145-161 (1989).
6. Haylock DN, Nilsson SK. Osteopontin: A bridge between bone and blood. Br. J. Haematol. 134(5), 467-474 (2006)
7. Scatena M, Liaw L, Giachelli CM. Osteopontin: A multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler. Thromb. Vasc. Biol. 27(11), 2302-2309 (2007).
8. Reza S, Shaukat A, Arain TM, Riaz QS, Mahmud M. Expression of osteopontin in patients with thyroid dysfunction. PLoS ONE 8(2), 56533 (2013).
9. Standal T, Borset M, Sundan A. Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp. Oncol. 26(3), 179-184 (2004)
10. Gene card for SP11. www. genecards. org/
11. Fedarko NS, Jain A, Karadag A, Fisher LW. Three small integrin binding ligand N-linked glycoproteins (siblings) bind and activate specific matrix metalloproteinases. FASEB J. 18(6), 734-736 (2004).
12. Bellahcene A, Castronovo V, Ogbureke KU, Fisher LW, Fedarko NS. Small integrin-binding ligand N-linked glycoproteins (siblings): Multi-functional proteins in cancer. Nat. Rev. Cancer 8(3), 212-226 (2008).
13. Kazanecki CC, Uzwiak DJ, Denhardt DT. Control of osteopontin signaling and function by post-translational phosphorylation and protein folding. J. Cell. Biochem. 102(4), 912-924 (2007).
14. Kurzbach D, Platzer G, Schwarz TC, Henen MA, Konrat R, Hinderberger D. Cooperatie unfolding compact conformations of the intrinsically disordered protein osteopontin. Biochemistry 52(31), 5167-5175 (2013).
15. Kon S, Ikesue M, Kimura C, et al. Syndecan-4 protects against osteopontin-mediated acute hepatic injury by masking functional domains of osteopontin. J. Exp. Med. 205(1), 25-33 (2008).
16. Mukherjee BB, Nemir M, Beninati S, et al. Interaction of osteopontin with fibronectin and other extracellular matrix molecules. Ann. NY Acad. Sci. 760, 201-212 (1995).
17. Chen Y, Bal BS, Gorski JP. Calcium and collagen binding properties of osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 from bone. J. Biol. Chem. 267(34), 24871-24878 (1992).
18. Martin SM, Schwartz JL, Giachelli CM, Ratner BD. Enhancing the biological activity of immobilized osteopontin using a type-1 collagen affinity coating. J. Biomed. Mater. Res. A 70(1), 10-19 (2004).
19. Shevde LA, Samant RS. Role of osteopontin in the pathophysiology of cancer. Matrix Biol. 37, 131-141 (2014)
20. Anborgh PH, Mutrie JC, Tuck AB, Chambers AF. Pre-A nd post-translational regulation of osteopontin in cancer. J. Cell. Commun. Signal. 5(2), 111-122 (2011).
21. Sainger R, Grau JB, Poggio P, et al. Dephosphorylation of circulating human osteopontin correlates with severe valvular calcification in patients with calcific aortic valve disease. Biomarkers 17(2), 111-118 (2012).
22. Gimba ER, Tilli TM. Human osteopontin splicing isoforms: Known roles, potential clinical applications and activated signaling pathways. Cancer Lett. 331(1), 11-17 (2013).
23. Shinohara ML, Kim HJ, Kim JH, Garcia VA, Cantor H. Alternative translation of osteopontin generates intracellular and secreted isoforms that mediate distinct biological activities in dendritic cells. Proc. Natl Acad. Sci. USA 105(20), 7235-7239 (2008).
24. Brown LF, Berse B, Van de Water L, et al. Expression and distribution of osteopontin in human tissues: Widespread association with luminal epithelial surfaces. Mol. Biol. Cell. 3(10), 1169-1180 (1992).
25. Rangaswami H, Bulbule A, Kundu GC. Osteopontin: Role in cell signaling and cancer progression. Trends Cell Biol. 16(2), 79-87 (2006).
26. Wai PY, Kuo PC. The role of osteopontin in tumor metastasis. J. Surg. Res. 121(2), 228-241 (2004).
27. O'Regan AW, Chupp GL, Lowry JA, Goetschkes M, Mulligan N, Berman JS. Osteopontin is associated with T cells in sarcoid granulomas and has T cell adhesive and cytokine-like properties in vitro. J. Immunol. 162(2), 1024-1031 (1999).
28. Ricardo SD, Franzoni DF, Roesener CD, Crisman JM, Diamond JR. Angiotensinogen and AT (1) antisense inhibition of osteopontin translation in rat proximal tubular cells. Am. J. Physiol. Renal. Physiol. 27(5), 708-716 (2000).
29. Hullinger TG, Pan Q, Viswanathan HL, Somerman MJ. TGFbeta and BMP-2 acivatin of the OPN promoter: Roles of smad-A nd hox-binding elements. Exp. Cell. Res. 262(1), 69-74 (2001).
30. Kale S, Raja R, Thorat D, Soundararajan G, Patil TV, Kundu GC. Osteopontin signaling upregulates cyclooxygenase-2 expression in tumor-associated macrophages leading to enhanced angiogenesis and melanoma growth via alpha9beta1 integrin. Oncogene 33(18), 2295-2306 (2014).
31. Raja R, Kale S, Thorat D, et al. Hypoxia-driven osteopontin contributes to breast tumor growth through modulation of HIF1alpha-mediated VEGF-dependent angiogenesis. Oncogene 33(16), 2053-2064 (2014).
32. Collins AR, Schnee J, Wang W, et al. Osteopontin modulates angiotensin II-induced fibrosis in the intact murine heart. J. Am. Coll. Cardiol. 43(9), 1698-1705 (2004).
33. Nomiyama T, Perez-Tilve D, Ogawa D, et al. Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J. Clin. Invest. 117(10), 2877-2888 (2007).
34. Inoue M, Shinohara ML. Intracellular osteopontin (iOPN) and immunity. Immunol. Res. 49(1-3), 160-172 (2011).
35. Chen Q, Shou P, Zhang L, et al. An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells. Stem Cells 32(2), 327-337 (2014).
36. Amir LR, Jovanovic A, Perdijk FBB, Toyosawa S, Everts V, Bronchers ALJJ. Immunolocalization of sibling and RUNX2 proteins during vertical distraction osteogenesis in the human mandible. J. Histochem. Cytochem. 55(11), 1095-1104 (2007).
37. Shen Q, Christakos S. The vitamin D receptor, Runx2, and the Notch signaling pathway cooperate in the transcriptional regulation of osteopontin. J. Biol. Chem. 280(49), 40589-40598 (2005).
38. Rittling SR, Matsumoto HN, McKee MD, et al. Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro. J. Bone Miner. Res. 13(7), 1101-1111 (1998).
39. Chellajah MA, Kizer N, Biswas R, et al. Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression. Mol. Biol. Cell. 14(1), 173-189 (2003).
40. Steitz SA, Speer MY, McKee MD, et al. Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification. Am. J. Pathol. 161(6), 2035-2046 (2002).
41. Sato W, Tomita A, Ichikawa D, et al. CCR2(+)CCR5(+) T cells produce matrix metalloproteinase-9 and osteopontin in the pathogenesis of multiple sclerosis. J. Immunol. 189(10), 5057-5065 (2012).
42. Agnholt J, Kelsen J, Schack L, Hvas CL, Dahlerup JF, Sorensen ES. Osteopontin, a protein with cytokine-like properties, is associated with inflammation in Crohn's disease. Scand. J. Immunol. 65(5), 453-460 (2007).
43. Wong CK, Lit LC, Tam LS, Li EK, Lam CW. Elevation of plasma osteopontin concentration is correlated with disease in patients with systemic lupus erythematosus. Rheumatology (Oxford) 44(5), 602-606 (2005).
44. Xu L, Ma X, Wang Y, et al. The expression and pathophysiological role of osteopontin in Graves' disease. J. Clin. Endocrinol. Metab. 96(11), E1866-E1870 (2011).
45. Waller AH, Sanchez-Ross M, Kaluski E, Klapholz M. Osteopontin in cardiovascular disease: A potential therapeutic target. Cardiol. Rev. 18(3), 125-131 (2010).
46. Liaw L, Lombardi DM, Almeida MM, Schwartz SM, de Blois D, Giachelli CM. Neutralizing antibodies directed against osteopontin inhibit rat caotid neointimal thickening after endothelial denudation. Arterioscler. Thromb. Vasc. Biol. 17(1), 188-193 (1997).
47. Bruemmer D, Collins AR, Noh G, et al. Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated is osteopontin-deficient mice. J. Clin. Invest. 112(9), 1318-1331 (2003).
48. Psarras S, Mayroidis M, Sanoudou D, et al. Regulation of adverse remodeling by osteopontin in a genetic heart failure model. Eur. Heart. J. 33(15), 1954-1963 (2012).
49. Kiefer FW, Zeyda M, Gollinger K, et al. Neutralization of osteopontin inhibits obesity-induced inflammation and insulin resistance. Diabetes 59(4), 935-946 (2010).
50. Atkins KB, Berry JE, Zhang WZ, et al. Coordinate expression of OPN and associated receptors during monocyte/macrophage differentiation of HL-60 cells. J. Cell. Physiol. 175, 229-237 (1998).
51. Denhardt DT, Noda M, O'Regan AW, Pravlin D, Berman J. Osteopontin as a means to cope with environmental insults: Regulation of inflammation, tissue remodeling and cell survival. J. Clin. Invest. 107(9), 1055-1061 (2001).
52. Wang KX, Denhardt DT. Osteopontin: Role in immune regulation and stress responses. Cytokine Growth Factor Rev. 19(5-6), 333-345 (2008).
53. Nagasaka A, Matsue H, Matsushima H, et al. Osteopontin is produced by mast cells and affects IgE-mediated degranulation and migration of mast cells. Eur. J. Immunol. 38(2), 489-499 (2008).
54. Burdo TH, Wood MR, Fox HS. Osteopontin prevents monocyte recirculation and apoptosis. J. Leukoc. Biol. 81(6), 1504-1511 (2007).
55. Scatena M, Almeida M, Chaisson ML, Fausto N, Nicosia RF, Giachelli CM. NF-KB mediates avh3 integrin-induced endothelial cell survival. J. Cell. Biol. 141, 1083-1093 (1998).
56. Gursoy G, Acar Y, Alagoz S. Osteopontin: A multifunctional molecule. J. Med. Med. Sci. 1(3), 055-060 (2010).
57. Kawamura K, Iyonaga K, Ichiyasu H, Nagano J, Suga M, Sasaki Y. Differentiation, maturation, and survival of dendritic cells by osteopontin regulation. Clin. Diagn. Lab. Immunol. 12(1), 206-212 (2005).
58. Mi Z, Guo H, Wai PY, Gao C, Kuo PC. Integrin-linked kinase regulates osteopontin-dependent MMP-2 and uPA expression to convey metastatic function in murine mammary epithelial cancer cells. Carcinogenesis 27(6), 1134-1145 (2006).
59. Rittling SR, Chambers AF. Role of osteopontin in tumour progression. Br. J. Cancer 90(10), 1877-1881 (2004)
60. Sharp JA, Sung V, Slavin J, Thompson EW, Henderson MA. Tumor cells are the source of osteopontin and bone sialoprotein expression in human breast cancer. Lab. Invest. 79(7), 869-877 (1999).
61. Gillespie MT, Thomas RJ, Pu ZY, Zhou H, Martin TJ, Findlay DM. Calcitonin receptors, bone sialoprotein and osteopontin are expressed in primary breast cancers. Int. J. Cancer 73(6), 812-815 (1997).
62. Brown LF, Papadopoulos-Sergiou A, Berse B, et al. Osteopontin expression and distribution in human carcinomas. Am. J. Pathol. 145(3), 610-623 (1994).
63. Lin CN, Wang CJ, Chao YJ, Lai MD, Shan YS. The significance of the co-existence of osteopontin and tumorassociated macrophages in gastric cancer progression. BMC Cancer 15, 128 (2015).
64. Zhao J, Dong L, Lu B, et al. Down-regulation of osteopontin suppresses growth and metastasis of hepatocellular carcinoma via induction of apoptosis. Gastroenterology 135(3), 956-968 (2008).
65. Shijubo N, Uede T, Kon S, Nagata M, Abe S. Vascular endothelial growth factor and osteopontin in tumor biology. Crit. Rev. Oncog. 11(2), 135-146 (2000).
66. Senger DR, Perruzzi CA, Papadopoulos-Sergiou A, Van de Water L. Adhesive properties of osteopontin: Regulation by a naturally occurring thrombin-cleavage in close proximity to the GRGDS cell-binding domain. Mol. Biol. Cell. 5(5), 565-574 (1994).
67. Senger DR, Ledbetter SR, Claffey KP, Papadopoulos-Sergiou A, Perruzzi CA, Detmar M. Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin. Am. J. Pathol. 149(1), 293-305 (1996).
68. Junaid A, Moon MC, Harding GEJ, Zahradka P. Osteopontin localizes to the nucleus of 293 cells and associates with p1-like kinase-1. Am. J. Physiol. Cell Physiol. 292(2), 919-926 (2007).
69. Dai J, Peng L, Fan K, et al. Osteopontin induces angiogenesis through activation of PI3K/AKT and ERK1/2 in endothelial cells. Oncogene 28(38), 3412-3422 (2009).
70. Crawford HC, Matrisian LM, Liaw L. Distinct roles of osteopontin in host defense activity and tumor survival during squamous cell carcinoma progression in vivo. Cancer Res. 58(22), 5206-5215 (1998).
71. Xuan JW, Hota C, Shigeyama Y, D'Errico JA, Somerman MJ, Chambers AF. Site-directed mutagenesis of the arginine-glycine-aspartic acid sequence in osteopontin destroys cell adhesion and migration functions. J. Cell. Biochem. 57(4), 680-690 (1995).
72. Senger DR, Perruzzi CA, Gracey CF, Papadopoulos A, Tenen DG. Secreted phosphoproteins associated with neoplastic transformation: Close homology with plasma proteins cleaved during blood coagulation. Cancer Res. 48(20), 5770-5774 (1988).
73. Terpos E, Kiagia M, Karapanagiotou EM, et al. The clinical significance of serum markers of bone turnover in NSCLC patients: Surveillance, management and prognostic implications. Anticancer Res. 29(5), 1651-1657 (2009).
74. Tuck AB, Chambers AF, Allan AL. Osteopontin overexpression in breast cancer: Knowledge gained and possible implications for clinical management. J. Cell. Biochem. 102(4), 859-868 (2007).
75. Wai PY, Kuo PC. Osteopontin: Regulation in tumor metastasis. Cancer Metastasis Rev. 27(1), 103-118 (2008).
76. Weber GF, Lett GS, Haubein NC. Osteopontin is a marker for cancer aggressiveness and patient survival. Br. J. Cancer 103(6), 861-869 (2010).
77. Ng L, Wan T, Chow A, et al. Osteopontin overexpression induced tumor progression and chemoresistance to oxaliplatin through induction of stem-like properties in human colorectal cancer. Stem. Cells Int. 2015, 247892 (2015).
78. Sreekanthreddy P, Srinivasan H, Kumar DM, et al. Identification of potential serum biomarkers of glioblastoma: Serum osteopontin levels correlate with poor prognosis. Cancer Epidemiol. Biomarkers Prev. 19(6), 1409-1422 (2010).
79. Song J, Ge Z, Yang X, et al. Hepatic stellate cells activated by acidic tumor microenvironment promote the metastasis of hepatocellular carcinoma via osteopontin. Cancer Lett. 356(2 pt B), 713-720 (2015).
80. Rud AK, Boye K, Oijordsbakken M, et al. Osteopontin is a prognostic biomarker in non-small cell lung cancer. BMC Cancer 13, 540 (2013).
81. Bache M, Kappler M, Wichmann H, et al. Elevated tumor and serum levels of the hypoxia-associated protein osteopontin are associated with prognosis for soft tissue sarcoma patients. BMC Cancer 10, 132 (2010)
82. Bramwell VH, Tuck AB, Wilson SM, et al. Expression of osteopontin and HGF/met in adult soft tissue tumors. Cancer Biol. Ther. 4(12), 1336-1341 (2005).
83. Liersch R, Gerss J, Schliemann C. Osteopontin is a prognostic factor for survival of acute myeloid leukemia patients. Blood 119(22), 5215-5220 (2012).
84. Fang XM, Pan XH, Chen M, Zeng WW, Li Y. Expression of osteopontin in central nervous system leukemia and its clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 21(2), 325-328 (2013).
85. Incesoy-Ozdemir S, Sahin G, Bozkurt C, Oren AC, Balkaya E. The relationship between cerebrospinal fluid osteopontin level and central nervous system involvement in childhood acute leukemia. Turk. J. Pediatr. 55(1), 42-49 (2013).
86. Mehde AA, Mehdi WA, Ali KF. Serum osteopontin growth hormone, and other biochemical parameters in children with acute lymphoblastic leukemia. J. Adv. Chem. 7(1), 1169-1174 (2014).
87. Elli M, Dagdemir A, Bozkurt C, et al. Serum osteopontin and CD44 levels in lymphoreticular malignancies in children. Bratisl. Lek. Listy 113(9), 534-538 (2012).
88. Allen CE, Li L, Peters TL, et al. Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared to epidermal Langerhans cells. J. Immunol. 184(8), 4557-4567 (2010).
89. Oh Y, Morimoto A, Shioda Y, et al. High serum osteopontin levels in pediatric patients with high risk Langerhans cell histiocytosis. Cytokine 70(2), 194-197 (2014).
90. Han YP, Ma CK, Wang SQ, et al. Evaluation of osteopontin as a potential biomarker for central nervous system embryonal tumors. J. Neurooncol. 119(2), 343-351 (2014).
91. Kao CL, Chiou SH, Chen YJ. Increased expression of osteopontin gene in atypical teratoid/rhabdoid tumor of the central nervous system. Modern Pathol. 18(6), 769-778 (2005).
92. Colin C, Baeza N, Bartoli C, et al. Identification of genes diferentially expressed in glioblastoma versus pilocytic astrocytoma using suppressive subtractive hybridization. Oncogene 25(19), 2818-2826 (2006).
93. Dalla-Torre CA, Yoshimoto M, Chung-Hae Lee CH, et al. Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma. BMC Cancer 6, 237 (2006).
94. Wong IHN, Chan AT, Johnson PJ. Quantitative analysis of circulating tumor cells in peripheral blood of osteosarcoma patients using osteoblast-specific messenger RNA markers: A pilot study. Clin. Cancer. Res. 6(6), 2183-2188 (2000).
95. Sulzbacher I, Birner P, Trieb K, Lang S, Chott A. Expression of osteopontin and vascular endothelial growth factor in benign and malignant bone tumors. Virchows Arch. 441(4), 345-349 (2002)
96. Endo-Munoz L, Cumming A, Sommerville S, Dickinson I, Saunders NA. Osteosarcoma is characterised by reduced expression of markers of osteoclastogenesis and antigen presentation compared with normal bone. Br. J. Cancer 103(1), 73-81 (2010).
97. Gadd S, Sredni ST, Huang CC, Perlman EJ. Rhabdoid tumor: Gene expression clues to pathogenesis and potential therapeutic targets. Lab. Invest. 90(5), 724-738 (2010).
98. Yang G, Xu YH, Chen HX, Wang XJ. Acute lymphoblastic leukemia cells inhibit the differentiation of bone mesenchymal stem cells into osteoblasts in vitro by activating notch signaling. Stem Cells Int. 2015, 162410 (2015).
99. Boyerinas B, Zafrir M, Yesilkanal AE, Price TT, Hyjek EM, Sipkins DA. Adhesion to osteopontin in the bone marrow niche regulates lymphoblastic leukemia cell dormancy. Blood 121(24), 4821-4831 (2013).
100. Stier S, Ko Y, Forkert R, et al. Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size. JEM 201(11), 1781-1791 (2005).
101. Sipkins DA, Wei X, Wu JW, et al. In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment. Nature 435(7044), 969-973 (2005).
102. Burger JA, Bürkle A. The CXCR4 chemokine receptor in acute and chronic leukaemia: A marrow homing receptor and potential therapeutic target. Br. J. Haematol. 137(4), 288-296 (2007).
103. Komori T. Runx2, a multifunctional transcription factor in skeletal development. J. Cell Biochem. 87(1), 1-8 (2002).
104. Flamant S, Kortulewski T, Dugary A, Bonnet ML, Guillier M, Guilhot F. Osteopontin is upregulated by BCR-ABL. Biochem. Biophysic. Res. Commun. 333, 1378-1384 (2005).
105. Vejda S, Piwock M, McKenna SL, Cotter TG. Autocrine secretions of osteopontin results in deregulation of I kappa B in BCR-ABL expressing cells. Br. J. Haematol. 128(5), 711-721 (2005).
106. Heiba NM, Elshazly SA. Expression and significance of osteopontin and its receptor CD44v6 in acute myeloid leukemia. Egypt. J. Haematol. 38, 108-114 (2013).
107. Iwanaga Y, Ueno M, Ueki M, et al. The expression of osteopontin is increased in vessels with blood-brain barrier impairment. Neuropathol. Appl. Neurobiol. 34(2), 145-154 (2008).
108. Ding Q, Stewart J, Prince CW, et al. Promotion of malignant astrocytoma cell migration by osteopontin expressed in the normal brain: Differences in integrin signaling during cell adhesion to osteopontin versus vitronectin. Cancer Res. 62(18), 5336-5343 (2002).
109. Saitoh Y, Kuratsu JI, Takeshima H, Yamamoto S, Ushio Y. Expression of osteopontin in human glioma. Its correlation with the malignancy. Lab. Invest. 72(1), 55-63 (1995).
110. Russell MD, Young AMH, Karr SK. Biomarkers of pediatric brain tumors. Front. Pediatr. 1, 7 (2013).
111. Li YS, Deng LZ, Zeng C, Lei GH. Role of osteopontin in osteosarcoma. Med. Oncol. 32(1), 449 (2015)
112. Luo X, Chen J, Song WX, et al. Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects. Lab. Invest. 88(12), 1264-1277 (2008).
113. Tang N, Song WX, Luo J, Haydon RC, He TC. Osteosarcoma development and stem cell differentiation. Clin. Orthop. Relat. Res. 466(9), 2114-2130 (2008).
114. Engin F, Bertin T, Ma O, et al. Notch signaling contributes to the pathogenesis of human osteosarcomas. Hum. Mol. Genet. 18(8), 1464-1470 (2009).
115. Kappler M, Kotzsch M, Bartel F, et al. Elevated expression level of survivin protein in soft-tissue sarcomas is a strong independent predictor of survival. Clin. Cancer. 9(3), 1098-1104 (2003).
116. Gao YA, Agnihotri R, Vary CP, et al. Expression and characterization of recombinant osteopontin peptides representing matrix metalloproteinase proteolytic fragments. Matrix Biol. 23(7), 457-466 (2004).