Skip to main content

Advertisement

SpringerLink
Log in

Osteopontin expression in co-cultures of human squamous cell carcinoma-derived cells and osteoblastic cells and its effects on the neoplastic cell phenotype and osteoclastic activation

  • Original Article
  • Published:
Tumor Biology

Abstract

This study evaluated the temporal expression of osteopontin (OPN) in co-cultures of human osteoblastic cells (SAOS-2) and oral squamous cell carcinoma (OSCC)-derived cells (SCC9) and examined the effects of osteoblast-derived OPN on the neoplastic cell phenotype. Additionally, the effects of these co-cultures on subsequent osteoclastic activity were explored. SCC9 cells were plated on Transwell® membranes that were either coated or not coated with Matrigel and were then co-cultured with SAOS-2 cells during the peak of OPN expression. SCC9 cells exposed to OPN-silenced SAOS-2 cultures and SCC9 cells cultured alone served as controls. SCC9 cells were quantitatively evaluated for cell adhesion, proliferation, migration, and invasion into Matrigel. The impact of co-culturing SAOS-2 and SCC9 cells on the resorptive capacity of U-937-derived osteoclastic cells was also investigated. Furthermore, a reciprocal induction of SAOS-2 and SCC9 cells in terms of OPN expression over the co-culture interval was identified. SAOS-2-secreted OPN altered the SCC9 cell phenotype, leading to enhanced cell adhesion and proliferation and higher Matrigel invasion. This invasion was also enhanced, albeit to a lesser degree, by co-culture with OPN-silenced SAOS-2 cells. Cell migration was not affected. Co-culture with SAOS-2 cells—mainly during the period of peak OPN expression—promoted over-expression of IL-6 and IL-8 by SCC9 cells and enhanced the resorptive capacity of osteoclastic cells. Taken together, these results suggest that osteoblast-derived OPN affects the interactions among OSCC-derived epithelial cells, osteoblasts, and osteoclasts, which could contribute to the process of bone destruction during bone invasion by OSCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Saman DM. A review of the epidemiology of oral and pharyngeal carcinoma: update. Head Neck Oncol. 2012;4:1.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Simard EP, Torre LA, Jemal A. International trends in head and neck cancer incidence rates: differences by country, sex and anatomic site. Oral Oncol. 2014;50:387–403.

    Article  PubMed  Google Scholar 

  3. Lichtenstein AV. Cancer: evolutionary, genetic and epigenetic aspects. Clin Epigenetics. 2010;1:85–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  5. Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014;15:786–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kellermann MG, Sobral LM, da Silva SD, Zecchin KG, Graner E, Lopes MA, et al. Mutual paracrine effects of oral squamous cell carcinoma cells and normal oral fibroblasts: induction of fibroblast to myofibroblast transdifferentiation and modulation of tumor cell proliferation. Oral Oncol. 2008;44:509–17.

    Article  CAS  PubMed  Google Scholar 

  7. Sobral LM, Zecchin KG, Nascimento de Aquino S, Lopes MA, Graner E, et al. Isolation and characterization of myofibroblast cell lines from oral squamous cell carcinoma. Oncol Rep. 2011;25:1013–20.

    CAS  PubMed  Google Scholar 

  8. Sobral LM, Bufalino A, Lopes MA, Graner E, Salo T, Coletta RD. Myofibroblasts in the stroma of oral cancer promote tumorigenesis via secretion of activin A. Oral Oncol. 2011;47:840–6.

    Article  CAS  PubMed  Google Scholar 

  9. Shevde LA, Samant RS, Paik JC, Metge BJ, Chambers AF, Casey G, et al. Osteopontin knockdown suppresses tumorigenicity of human metastatic breast carcinoma, MDA-MB-435. Clin Exp Metastasis. 2006;23:123–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Senger DR, Wirth DF, Hynes RO. Transformed mammalian cells secrete specific proteins and phosphoproteins. Cell. 1979;16:885–93.

    Article  CAS  PubMed  Google Scholar 

  11. Franzén A, Heinegård D. Isolation and characterization of two sialoproteins present only in bone calcified matrix. Biochem J. 1985;232:715–24.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Weber GF, Cantor H. The immunology of Eta-1/osteopontin. Cytokine Growth Factor Rev. 1996;7:241–8.

    Article  CAS  PubMed  Google Scholar 

  13. Brown LF, Berse B, Van de Water L, Papadopoulos-Sergiou A, Perruzzi CA, Manseau EJ, et al. Expression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces. Mol Biol Cell. 1992;3:1169–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Denhardt DT, Guo X. Osteopontin: a protein with diverse functions. FASEB J. 1993;7:1475–82.

    CAS  PubMed  Google Scholar 

  15. Bautista DS, Denstedt J, Chambers AF, Harris JF. Low-molecular-weight variants of osteopontin generated by serine proteinases in urine of patients with kidney stones. J Cell Biochem. 1996;61:402–9.

    Article  CAS  PubMed  Google Scholar 

  16. Chen RX, Xia YH, Xue TC, Ye SL. Osteopontin promotes hepatocellular carcinoma invasion by up-regulating MMP-2 and uPA expression. Mol Biol Rep. 2011;38:3671–7.

    Article  CAS  PubMed  Google Scholar 

  17. Lu JG, Li Y, Li L, Kan X. Overexpression of osteopontin and integrin αv in laryngeal and hypopharyngeal carcinomas associated with differentiation and metastasis. J Cancer Res Clin Oncol. 2011;137:1613–8.

    Article  CAS  PubMed  Google Scholar 

  18. Wang ZM, Cui YH, Li W, Chen SY, Liu TS. Lentiviral-mediated siRNA targeted against osteopontin suppresses the growth and metastasis of gastric cancer cells. Oncol Rep. 2011;25:997–1003.

    CAS  PubMed  Google Scholar 

  19. Zhang R, Pan X, Huang Z, Weber GF, Zhang G. Osteopontin enhances the expression and activity of MMP-2 via the SDF-1/CXCR4 axis in hepatocellular carcinoma cell lines. PLoS One. 2011;6:e23831.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Matsuzaki H, Shima K, Muramatsu T, Ro Y, Hashimoto S, Shibahara T, et al. Osteopontin as biomarker in early invasion by squamous cell carcinoma in tongue. J Oral Pathol Med. 2007;36:30–4.

    Article  CAS  PubMed  Google Scholar 

  21. Routray S, Kheur SM, Kheur M. Osteopontin: a marker for invasive oral squamous cell carcinoma but not for potentially malignant epithelial dysplasias. Ann Diagn Pathol. 2013;17:421–4.

    Article  PubMed  Google Scholar 

  22. Weber GF, Lett GS, Haubein NC. Osteopontin is a marker for cancer aggressiveness and patient survival. Br J Cancer. 2010;103:861–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Avirović M, Matušan-Ilijaš K, Damante G, Fabrro D, Cerović R, Juretić M, et al. Osteopontin expression is an independent factor for poor survival in oral squamous cell carcinoma: a computer-assisted analysis on TMA sections. J Oral Pathol Med. 2013;42:620–6.

    Article  PubMed  Google Scholar 

  24. Ingale Y, Routray S, Kheur SM, Kheur M, Mohanty N. Evaluating the efficacy of osteopontin expression as a prognostic marker in oral squamous cell carcinoma in the Indian subpopulation. J Oral Maxillofac Pathol. 2014;18(Suppl 1):S11–5.

    PubMed  PubMed Central  Google Scholar 

  25. Sodek J, Ganss B, McKee MD. Osteopontin. Crit Rev Oral Biol Med. 2000;11:279–303.

    Article  CAS  PubMed  Google Scholar 

  26. Standal T, Borset M, Sundan A. Role of osteopontin in adhesion, migration, cell survival and bone remodeling. Exp Oncol. 2004;26:179–84.

    CAS  PubMed  Google Scholar 

  27. Hunter GK. Role of osteopontin in modulation of hydroxyapatite formation. Calcif Tissue Int. 2013;93:348–54.

    Article  CAS  PubMed  Google Scholar 

  28. Semba I, Matsuuchi H, Miura Y. Histomorphometric analysis of osteoclastic resorption in bone directly invaded by gingival squamous cell carcinoma. J Oral Pathol Med. 1996;25:429–35.

    Article  CAS  PubMed  Google Scholar 

  29. Guise TA, Mundy GR. Cancer and bone. Endocr Rev. 1998;19:18–54.

    CAS  PubMed  Google Scholar 

  30. Chellaiah MA, Kizer N, Biswas R, Alvarez U, Strauss-Schoenberger J, Rifas L, et al. Osteopontin deficiency produces osteoclast dysfunction due to reduced CD44 surface expression. Mol Biol Cell. 2003;14:173–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li M, Amizuka N, Takeuchi K, Freitas PH, Kawano Y, Hoshino M, et al. Histochemical evidence of osteoclastic degradation of extracellular matrix in osteolytic metastasis originating from human lung small carcinoma (SBC-5) cells. Microsc Res Tech. 2006;69:73–83.

    Article  CAS  PubMed  Google Scholar 

  32. Kruger TE, Miller AH, Godwin AK, Wang J. Bone sialoprotein and osteopontin in bone metastasis of osteotropic cancers. Crit Rev Oncol Hematol. 2014;89:330–41.

    Article  PubMed  Google Scholar 

  33. Jimi E, Furuta H, Matsuo K, Tominaga K, Takahashi T, Nakanishi O. The cellular and molecular mechanisms of bone invasion by oral squamous cell carcinoma. Oral Dis. 2011;17:462–8.

    Article  CAS  PubMed  Google Scholar 

  34. Amoui M, Suhr SM, Baylink DJ, Lau KH. An osteoclastic protein-tyrosine phosphatase may play a role in differentiation and activity of human monocytic U-937 cell-derived, osteoclast-like cells. Am J Phys Cell Phys. 2004;287:C874–84.

    Article  CAS  Google Scholar 

  35. Schwartz Fo HO, Novaes Jr AB, de Castro LM, Rosa AL, de Oliveira PT. In vitro osteogenesis on a microstructured titanium surface with additional submicron-scale topography. Clin Oral Implants Res. 2007;18:333–44.

    Article  PubMed  Google Scholar 

  36. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25:402–8.

    Article  CAS  PubMed  Google Scholar 

  37. de Oliva MA, Maximiano WM, de Castro LM, da Silva Jr PE, Fernandes RR, Ciancaglini P, et al. Treatment with a growth factor-protein mixture inhibits formation of mineralized nodules in osteogenic cell cultures grown on titanium. J Histochem Cytochem. 2009;57:265–76.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Wai PY, Kuo PC. Osteopontin: regulation in tumor metastasis. Cancer Metastasis Rev. 2008;27:103–18.

    Article  CAS  PubMed  Google Scholar 

  39. Terpos E, Kiagia M, Karapanagiotou EM, Charpidou A, Dilana KD, Nasothimiou E, et al. The clinical significance of serum markers of bone turnover in NSCLC patients: surveillance, management and prognostic implications. Anticancer Res. 2009;29:1651–7.

    CAS  PubMed  Google Scholar 

  40. Weber GF, Lett GS, Haubein NC. Categorical meta-analysis of osteopontin as a clinical cancer marker. Oncol Rep. 2011;25:433–41.

    Article  PubMed  Google Scholar 

  41. Mardani M, Andisheh-Tadbir A, Khademi B, Fattahi MJ, Shafiee S, Asad-Zadeh M. Serum levels of osteopontin as a prognostic factor in patients with oral squamous cell carcinoma. Tumour Biol. 2014;35:3827–9.

    Article  CAS  PubMed  Google Scholar 

  42. Buijs JT, van der Pluijm G. Osteotropic cancers: from primary tumor to bone. Cancer Lett. 2009;273:177–93.

    Article  CAS  PubMed  Google Scholar 

  43. Samuvel DJ, Sundararaj KP, Li Y, Lopes-Virella MF, Huang Y. Adipocyte-mononuclear cell interaction, toll-like receptor 4 activation, and high glucose synergistically up-regulate osteopontin expression via an interleukin 6-mediated mechanism. J Biol Chem. 2010;285:3916–27.

    Article  CAS  PubMed  Google Scholar 

  44. Fried D, Mullins B, Weissler M, Shores C, Zanation A, Hackman T, et al. Prognostic significance of bone invasion for oral cavity squamous cell carcinoma considered T1/T2 by American joint committee on cancer size criteria. Head Neck. 2014;36:776–81.

    Article  PubMed  Google Scholar 

  45. Miki Y, Ono K, Hata S, Suzuki T, Kumamoto H, Sasano H. The advantages of co-culture over mono cell culture in simulating in vivo environment. J Steroid Biochem Mol Biol. 2012;131:68–75.

    Article  CAS  PubMed  Google Scholar 

  46. Gao C, Guo H, Downey L, Marroquin C, Wei J, Kuo PC. Osteopontin-dependent CD44v6 expression and cell adhesion in HepG2 cells. Carcinogenesis. 2003;24:1871–8.

    Article  CAS  PubMed  Google Scholar 

  47. Lyons AJ, Jones J. Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma. Int J Oral Maxillofac Surg. 2007;36:671–9.

    Article  CAS  PubMed  Google Scholar 

  48. Harada T, Shinohara M, Nakamura S, Oka M. An immunohistochemical study of the extracellular matrix in oral squamous cell carcinoma and its association with invasive and metastatic potential. Virchows Arch. 1994;424:257–66.

    Article  CAS  PubMed  Google Scholar 

  49. Clëzardin P. Integrins in bone metastasis formation and potential therapeutic implications. Curr Cancer Drug Targets. 2009;9:801–6.

    Article  PubMed  Google Scholar 

  50. Schneider JG, Amend SR, Weilbaecher KN. Integrins and bone metastasis: integrating tumor cell and stromal cell interactions. Bone. 2011;48:54–65.

    Article  CAS  PubMed  Google Scholar 

  51. Angelucci A, Festuccia C, Gravina GL, Muzi P, Bonghi L, Vicentini C, et al. Osteopontin enhances the cell proliferation induced by the epidermal growth factor in human prostate cancer cells. Prostate. 2004;59:157–66.

    Article  CAS  PubMed  Google Scholar 

  52. Nam TJ, Busby Jr WH, Rees C, Clemmons DR. Thrombospondin and osteopontin bind to insulin-like growth factor (IGF)-binding protein-5 leading to an alteration in IGF-I-stimulated cell growth. Endocrinology. 2000;141:1100–6.

    CAS  PubMed  Google Scholar 

  53. Duan C, Xu Q. Roles of insulin-like growth factor (IGF) binding proteins in regulating IGF actions. Gen Comp Endocrinol. 2005;142:44–52.

    Article  CAS  PubMed  Google Scholar 

  54. Zhi X, Lamperska K, Golusinski P, Schork NJ, Luczewski L, Golusinski W, et al. Expression levels of insulin-like growth factors 1 and 2 in head and neck squamous cell carcinoma. Growth Hormon IGF Res. 2014;24:137–41.

    Article  CAS  Google Scholar 

  55. Martinez C, Churchman M, Freeman T, Ilyas M. Osteopontin provides early proliferative drive and may be dependent upon aberrant c-myc signalling in murine intestinal tumours. Exp Mol Pathol. 2010;88:272–7.

    Article  CAS  PubMed  Google Scholar 

  56. Fukuda M, Hamao A, Tanaka A, Kitada M, Suzuki S, Kusama K, et al. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/APO2L) and its receptors expression in human squamous cell carcinoma of the oral cavity. Oncol Rep. 2003;10:1113–9.

    CAS  PubMed  Google Scholar 

  57. Kassouf N, Thornhill MH. Oral cancer cell lines can use multiple ligands, including Fas-L, TRAIL and TNF-alpha, to induce apoptosis in Jurkat T cells: possible mechanisms for immune escape by head and neck cancers. Oral Oncol. 2008;44:672–82.

    Article  CAS  PubMed  Google Scholar 

  58. Polat B, Wohlleben G, Katzer A, Djuzenova CS, Technau A, Flentje M. Influence of osteopontin silencing on survival and migration of lung cancer cells. Strahlenther Onkol. 2013;189:62–7.

    Article  CAS  PubMed  Google Scholar 

  59. Zhang H, Guo M, Chen JH, Wang Z, Du XF, Liu PX, et al. Osteopontin knockdown inhibits αv,β3 integrin-induced cell migration and invasion and promotes apoptosis of breast cancer cells by inducing autophagy and inactivating the PI3K/Akt/mTOR pathway. Cell Physiol Biochem. 2014;33:991–1002.

    Article  CAS  PubMed  Google Scholar 

  60. Agnihotri R, Crawford HC, Haro H, Matrisian LM, Havrda MC, Liaw L. Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin). J Biol Chem. 2001;276:28261–7.

    Article  CAS  PubMed  Google Scholar 

  61. Gao YA, Agnihotri R, Vary CP, Liaw L. Expression and characterization of recombinant osteopontin peptides representing matrix metalloproteinase proteolytic fragments. Matrix Biol. 2004;23:457–66.

    Article  CAS  PubMed  Google Scholar 

  62. Chuang HC, Su CY, Huang HY, Huang CC, Chien CY, Du YY, et al. Active matrix metalloproteinase-7 is associated with invasion in buccal squamous cell carcinoma. Mod Pathol. 2008;21:1444–50.

    Article  CAS  PubMed  Google Scholar 

  63. Li TJ, Cui J. COX-2, MMP-7 expression in oral lichen planus and oral squamous cell carcinoma. Asian Pac J Trop Med. 2013;6:640–3.

    Article  PubMed  Google Scholar 

  64. Mäkinen LK, Häyry V, Hagström J, Sorsa T, Passador-Santos F, Keski-Säntti H, et al. Matrix metalloproteinase-7 and matrix metalloproteinase-25 in oral tongue squamous cell carcinoma. Head Neck. 2014;36:1783–8.

    Article  PubMed  Google Scholar 

  65. Mashhadiabbas F, Mahjour F, Mahjour SB, Fereidooni F, Hosseini FS. The immunohistochemical characterization of MMP-2, MMP-10, TIMP-1, TIMP-2, and podoplanin in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;114:240–50.

    Article  PubMed  Google Scholar 

  66. Gao ZB, Duan YQ, Zhang L, Chen DW, Ding PT. Expression of matrix metalloproteinase 2 and its tissue inhibitor in oral squamous cell carcinoma. Int J Mol Med. 2005;16:599–603.

    CAS  PubMed  Google Scholar 

  67. Singh RD, Haridas N, Patel JB, Shah FD, Shukla SN, Shah PM, et al. Matrix metalloproteinases and their inhibitors: correlation with invasion and metastasis in oral cancer. Indian J Clin Biochem. 2010;25:250–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Singh RD, Nilayangode H, Patel JB, Shah FD, Shukla SN, Shah PM, et al. Combined evaluation of matrix metalloproteinases and their inhibitors has better clinical utility in oral cancer. Int J Biol Markers. 2011;26:27–36.

    Article  CAS  PubMed  Google Scholar 

  69. Pérez-Sayáns García M, Suárez-Peñaranda JM, Gayoso-Diz P, Barros-Angueira F, Gándara-Rey JM, García-García A. Tissue inhibitor of metalloproteinases in oral squamous cell carcinomas—a therapeutic target? Cancer Lett. 2012;323:11–9.

    Article  PubMed  Google Scholar 

  70. Bodnar M, Szylberg Ł, Kazmierczak W, Marszalek A. Tumor progression driven by pathways activating matrix metalloproteinases and their inhibitors. J Oral Pathol Med. 2015;44:437–43.

    Article  CAS  PubMed  Google Scholar 

  71. Li M, Wang Z, Xing Y, Yu J, Tian L, Zhang D, et al. A multicenter study on expressions of vascular endothelial growth factor, matrix metallopeptidase-9 and tissue inhibitor of metalloproteinase-2 in oral and maxillofacial squamous cell carcinoma. Iran Red Crescent Med J. 2014;16:e13185.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Brew K, Nagase H. The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim Biophys Acta. 1803;2010:55–71.

    Google Scholar 

  73. Erdem NF, Carlson ER, Gerard DA, Ichiki AT. Characterization of 3 oral squamous cell carcinoma cell lines with different invasion and/or metastatic potentials. J Oral Maxillofac Surg. 2007;65:1725–33.

    Article  PubMed  Google Scholar 

  74. Nakashima T, Yasumatsu R, Masuda M, Clayman GL, Komune S. Prognostic value of cathepsin L and its inhibitor headpin in oral squamous cell carcinoma. J Laryngol Otol. 2012;126:1134–7.

    Article  CAS  PubMed  Google Scholar 

  75. Bitu CC, Kauppila JH, Bufalino A, Nurmenniemi S, Teppo S, Keinänen M, et al. Cathepsin K is present in invasive oral tongue squamous cell carcinoma in vivo and in vitro. PLoS One. 2013;8:e70925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Duong LT, Wesolowski GA, Leung P, Oballa R, Pickarski M. Efficacy of a cathepsin k inhibitor in a preclinical model for prevention and treatment of breast cancer bone metastasis. Mol Cancer Ther. 2014;13:2898–909.

    Article  CAS  PubMed  Google Scholar 

  77. Deyama Y, Tei K, Yoshimura Y, Izumiyama Y, Takeyama S, Hatta M, et al. Oral squamous cell carcinomas stimulate osteoclast differentiation. Oncol Rep. 2008;20:663–8.

    CAS  PubMed  Google Scholar 

  78. Kayamori K, Sakamoto K, Nakashima T, Takayanagi H, Morita K, Omura K, et al. Roles of interleukin-6 and parathyroid hormone-related peptide in osteoclast formation associated with oral cancers: significance of interleukin-6 synthesized by stromal cells in response to cancer cells. Am J Pathol. 2010;176:968–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hwang YS, Lee SK, Park KK, Chung WY. Secretion of IL-6 and IL-8 from lysophosphatidic acid-stimulated oral squamous cell carcinoma promotes osteoclastogenesis and bone resorption. Oral Oncol. 2012;48:40–8.

  80. Bendre MS, Montague DC, Peery T, Akel NS, Gaddy D, Suva LJ. Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone. 2003;33:28–37.

    Article  CAS  PubMed  Google Scholar 

  81. Kudo O, Sabokbar A, Pocock A, Itonaga I, Fujikawa Y, Athanasou NA. Interleukin-6 and interleukin-11 support human osteoclast formation by a RANKL-independent mechanism. Bone. 2003;32:1–7.

    Article  CAS  PubMed  Google Scholar 

  82. Kwan Tat S, Padrines M, Théoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 2004;15:49–60.

    Article  PubMed  Google Scholar 

  83. Gilbert M, Giachelli CM, Stayton PS. Biomimetic peptides that engage specific integrin-dependent signaling pathways and bind to calcium phosphate surfaces. J Biomed Mater Res A. 2003;67:69–77.

    Article  PubMed  Google Scholar 

  84. Gilbert M, Shaw WJ, Long JR, Nelson K, Drobny GP, Giachelli CM, Stayton PS. Chimeric peptides of statherin and osteopontin that bind hydroxyapatite and mediate cell adhesion. J Biol Chem. 2000;275:16213–8.

    Article  CAS  PubMed  Google Scholar 

  85. Pietak AM, Sayer M. Functional atomic force microscopy investigation of osteopontin affinity for silicon stabilized tricalcium phosphate bioceramic surfaces. Biomaterials. 2006;27:3–14.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the State of Sao Paulo Research Foundation (FAPESP, grants #2012/07531-9, #2012/20863-0, and #2012/08605-6) and the National Council of Scientific and Technological Development (CNPq, grant #308200/2012-8) for financial support. Roger Rodrigo Fernandes and Fabíola Singaretti de Oliveira are acknowledged for technical assistance. The mouse monoclonal anti-rat osteopontin (MPIIIB10-1) antibody, developed by Michael Solursh and Ahnders Franzen, was obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242.

Author information

Authors and Affiliations

  1. Cell Culture Laboratory, Department of Morphology, Physiology and Basic Pathology, School of Dentistry of Ribeirão Preto, University of São Paulo, Av. do Café, s/n, Monte Alegre, Ribeirão Preto, São Paulo, 14040-904, Brazil

    Lucas Novaes Teixeira, Larissa Moreira Spinola de Castro Raucci, Gabriela Caroline Alonso, Adalberto Luiz Rosa & Paulo Tambasco de Oliveira

  2. Department of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas, Av. Limeira, 901, Vila Rezende, Piracicaba, São Paulo, 13414-903, Brazil

    Lucas Novaes Teixeira & Ricardo Della Coletta

Authors
  1. Lucas Novaes Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Larissa Moreira Spinola de Castro Raucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabriela Caroline Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ricardo Della Coletta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Adalberto Luiz Rosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paulo Tambasco de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Lucas Novaes Teixeira or Paulo Tambasco de Oliveira.

Ethics declarations

Funding

The State of Sao Paulo Research Foundation (FAPESP, Brazil), grants #2012/07531-9, #2012/20863-0, and #2012/08605-6, and the National Council of Scientific and Technological Development (CNPq, Brazil), grant #308200/2012-8.

Conflicts of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Teixeira, L.N., de Castro Raucci, L.M.S., Alonso, G.C. et al. Osteopontin expression in co-cultures of human squamous cell carcinoma-derived cells and osteoblastic cells and its effects on the neoplastic cell phenotype and osteoclastic activation. Tumor Biol. 37, 12371–12385 (2016). https://doi.org/10.1007/s13277-016-5104-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-5104-0

Keywords

Search

Navigation