Molecular and Cellular Biochemistry

, Volume 336, Issue 1–2, pp 65–74 | Cite as

Fibronectin–integrin mediated signaling in human cervical cancer cells (SiHa)

  • Gargi Maity
  • Shabana Fahreen
  • Aniruddha Banerji
  • Paromita Roy Choudhury
  • Triparna Sen
  • Anindita Dutta
  • Amitava Chatterjee
Article

Abstract

Interaction between cell surface integrin receptors and extracellular matrix (ECM) components plays an important role in cell survival, proliferation, and migration, including tumor development and invasion of tumor cells. Matrix metalloproteinases (MMPs) are a family of metalloproteinases capable of digesting ECM components and are important molecules for cell migration. Binding of ECM to integrins initiates cascades of cell signaling events modulating expression and activity of different MMPs. The aim of this study is to investigate fibronectin–integrin-mediated signaling and modulation of MMPs. Our findings indicated that culture of human cervical cancer cell (SiHa) on fibronectin-coated surface perhaps sends signals via fibronectin–integrin-mediated signaling pathways recruiting focal adhesion kinase (FAK) extracellular signal regulated kinase (ERK), phosphatidyl inositol 3 kinase (PI-3K), integrin-linked kinase (ILK), nuclear factor-kappa B (NF-κB), and modulates expression and activation of mainly pro-MMP-9, and moderately pro-MMP-2 in serum-free culture medium.

Keywords

Integrin α5β1 Fibronectin SiHa MMP-9 ERK PI-3K 

Notes

Acknowledgments

We acknowledge the financial support and inspiration received from Dr. Jaydip Biswas, Director, CNCI, and the financial support from Department of Science and Technology, New Delhi (Grant No. SR/SO/HS-59/2004).

References

  1. 1.
    Geiger B, Bershadsky A, Pankov R et al (2001) Transmembrane crosstalk between the extracellular matrix–cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2:793–805CrossRefPubMedGoogle Scholar
  2. 2.
    Danen EH, Yamada KM (2001) Fibronectin, integrins, and growth control. J Cell Physiol 189:1–13CrossRefPubMedGoogle Scholar
  3. 3.
    Ivaska J, Heino J (2000) Adhesion receptors and cell invasion: mechanisms of integrin-guided degradation of extracellular matrix. Cell Mol Life Sci 57:16–24CrossRefPubMedGoogle Scholar
  4. 4.
    Miyamoto S, Teramoto H, Coso OA et al (1995) Integrin function: molecular hierarchies of cytoskeletal and signaling molecules. J Cell Biol 131:791–805CrossRefPubMedGoogle Scholar
  5. 5.
    Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8:604–617CrossRefPubMedGoogle Scholar
  6. 6.
    Juliano RL (2002) Signal transduction by cell adhesion receptors and the cytoskeleton: functions of integrins, cadherins, selectins, and immunoglobulin-superfamily members. Annu Rev Pharmacol Toxicol 42:283–323CrossRefPubMedGoogle Scholar
  7. 7.
    Sawhney RS, Cookson MM, Omar Y et al (2006) Integrin alpha2-mediated ERK and calpain activation play a critical role in cell adhesion and motility via focal adhesion kinase signaling: identification of a novel signaling pathway. J Biol Chem 281:8497–8510CrossRefPubMedGoogle Scholar
  8. 8.
    Hill CS, Treisman R (1995) Transcriptional regulation by extracellular signals: mechanisms and specificity. Cell 80:199–211CrossRefPubMedGoogle Scholar
  9. 9.
    Seger R, Krebs EG (1995) The MAPK signaling cascade. FASEB J 9:726–735PubMedGoogle Scholar
  10. 10.
    Hannigan G, Troussard AA, Dedhar S (2005) Integrin-linked kinase: a cancer therapeutic target unique among its ILK. Nat Rev Cancer 5:51–63CrossRefPubMedGoogle Scholar
  11. 11.
    Hehlgans S, Haase M, Cordes N (2007) Signaling via integrins: implications for cell survival and anticancer strategies. Biochim Biophys Acta 1775:163–180PubMedGoogle Scholar
  12. 12.
    Hofmann UB, Westphal JR, Van Kraats AA et al (2000) Expression of integrin alpha (v) beta (3) correlates with activation of membrane-type matrix metalloproteinase-1 (MT1-MMP) and matrix metalloproteinase-2 (MMP-2) in human melanoma cells in vitro and in vivo. Int J Cancer 87:12–19CrossRefPubMedGoogle Scholar
  13. 13.
    Johansson S, Svineng G, Wennerberg K et al (1997) Fibronectin–integrin interactions. Front Biosci 2:126–146Google Scholar
  14. 14.
    Ruoslahti E (1999) Fibronectin and its integrin receptors in cancer. Adv Cancer Res 76:1–20CrossRefPubMedGoogle Scholar
  15. 15.
    Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174CrossRefPubMedGoogle Scholar
  16. 16.
    Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34CrossRefPubMedGoogle Scholar
  17. 17.
    Livant DL, Brabec RK, Pienta KJ et al (2000) Anti-invasive, antitumorigenic, and antimetastatic activities of the PHSCN sequence in prostate carcinoma. Cancer Res 60:309–320PubMedGoogle Scholar
  18. 18.
    Hocking DC, Sottile J, McKeown-Longo PJ (1998) Activation of distinct alpha5beta1-mediated signaling pathways by fibronectin’s cell adhesion and matrix assembly domains. J Cell Biol 141:241–253CrossRefPubMedGoogle Scholar
  19. 19.
    Jia Y, Zeng ZZ, Markwart SM et al (2004) Integrin fibronectin receptors in matrix metalloproteinase-1-dependent invasion by breast cancer and mammary epithelial cells. Cancer Res 64:8674–8681CrossRefPubMedGoogle Scholar
  20. 20.
    Han S, Ritzenthaler JD, Sitaraman SV et al (2006) Fibronectin increases matrix metalloproteinase 9 expression through activation of c-Fos via extracellular-regulated kinase and phosphatidylinositol 3-kinase pathways in human lung carcinoma cells. J Biol Chem 281:29614–29624CrossRefPubMedGoogle Scholar
  21. 21.
    Han S, Ritzenthaler JD, Wingerd B et al (2007) Extracellular matrix fibronectin increases prostaglandin E2 receptor subtype EP4 in lung carcinoma cells through multiple signaling pathways: the role of AP-2. J Biol Chem 282:7961–7972CrossRefPubMedGoogle Scholar
  22. 22.
    Thant AA, Nawa A, Kikkawa F et al (2000) Fibronectin activates matrix metalloproteinase-9 secretion via the MEK1-MAPK and the PI3K-Akt pathways in ovarian cancer cells. Clin Exp Metastasis 18:423–428CrossRefPubMedGoogle Scholar
  23. 23.
    Segarra M, Vilardell C, Matsumoto K et al (2005) Dual function of focal adhesion kinase in regulating integrin-induced MMP-2 and MMP-9 release by human T lymphoid cells. FASEB J 19:1875–1877CrossRefPubMedGoogle Scholar
  24. 24.
    Esparza J, Vilardell C, Calvo J et al (1999) Fibronectin upregulates gelatinase B (MMP-9) and induces coordinated expression of gelatinase A (MMP-2) and its activator MT1-MMP (MMP-14) by human T lymphocyte cell lines. A process repressed through RAS/MAP kinase signaling pathways. Blood 94:2754–2766PubMedGoogle Scholar
  25. 25.
    Das S, Banerji A, Frei E et al (2008) Rapid expression and activation of MMP-2 and MMP-9 upon exposure of human breast cancer cells (MCF-7) to fibronectin in serum free medium. Life Sci 82:467–476CrossRefPubMedGoogle Scholar
  26. 26.
    Mitra A, Chakrobarty J, Chatterjee A (2003) Binding of α5 monoclonal antibody to cell surface α5β1 integrin modulates MMP-2 and MMP-7 activity in B16F10 melanoma cells. J Environ Pathol Toxicol Oncol 22:167–178CrossRefPubMedGoogle Scholar
  27. 27.
    Mitra A, Chakrabarti J, Banerji A et al (2004) Binding of α2 monoclonal antibody to human cervical tumour cell (SiHa) surface α2β1 integrin modulates MMP-2 activity. Gynecol Oncol 94:33–39CrossRefPubMedGoogle Scholar
  28. 28.
    Chattopadhaya N, Mitra A, Frei E et al (2001) Human cervical tumor cell (SiHa) surface alphavbeta3 integrin receptor has associated matrix metalloproteinase (MMP-2) activity. J Cancer Res Clin Oncol 127:653–658Google Scholar
  29. 29.
    Bafetti LM, Young TN, Itoh Y et al (1998) Intact vitronectin induces matrix metalloproteinase-2 and tissue inhibitor of metalloproteinases-2 expression and enhanced cellular invasion by melanoma cells. J Biol Chem 273:143–149CrossRefPubMedGoogle Scholar
  30. 30.
    Rolli M, Fransvea E, Oilch J et al (2003) Activated integrin alphavbeta3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells. Proc Natl Acad Sci USA 100:9482–9487CrossRefPubMedGoogle Scholar
  31. 31.
    Mitra A, Chakrabarti J, Banerji A et al (2006) Culture of human cervical cancer cells, SiHa, in the presence of fibronectin activates MMP-2. J Cancer Res Clin Oncol 132:505–513CrossRefPubMedGoogle Scholar
  32. 32.
    Murillo CA, Rychahou PG, Evers BM (2004) Inhibition of α5 integrin decreases PI3K activation and cell adhesion of human colon cancer. Surgery 136:143–149CrossRefPubMedGoogle Scholar
  33. 33.
    Troussard AA, Costello P, Yoganathan TN et al (2000) The integrin linked kinase (ILK) induces an invasive phenotype via AP-1 transcription factor-dependent upregulation of matrix metalloproteinase 9 (MMP-9). Oncogene 19:5444–5452CrossRefPubMedGoogle Scholar
  34. 34.
    Chakrobarty J, Mitra A, Banerji A et al (2006) Culture of human fibrosarcoma HT-1080 cells in presence of fibronectin activates MMP-2. J Environ Pathol Toxicol Oncol 25:667–677Google Scholar
  35. 35.
    Kenny A, Kaur S, Coussens LM et al (2008) The initial steps of ovarian cancer cell metastasis are mediated by MMP-2 cleavage of vitronectin and fibronectin. J Clin Invest 118:1367–1379CrossRefPubMedGoogle Scholar
  36. 36.
    Banerji A, Das S, Chatterjee A (2008) Culture of human A375 melanoma cells in the presence of fibronectin causes expression of MMP-9 and activation of MMP-2 in culture supernatants. J Environ Pathol Toxicol Oncol 27:135–145PubMedGoogle Scholar
  37. 37.
    Kato Y, Yamashita T, Ishikawa M (2002) Relationship between expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and invasion ability of cervical cancer cells. Oncol Rep 9:565–569PubMedGoogle Scholar
  38. 38.
    Bannikov GA, Karelina TV, Collier IE et al (2002) Substrate binding of gelatinase B induces its enzymatic activity in the presence of intact propeptide. J Biol Chem 277:16022–16027CrossRefPubMedGoogle Scholar
  39. 39.
    Brew K, Dinakarpandian D, Nagase H (2000) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477:267–283PubMedGoogle Scholar
  40. 40.
    Wilhelm SM, Collier IE, Marmer BL et al (1989) SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem 264:17213–17221PubMedGoogle Scholar
  41. 41.
    Munshi HG, Stack MS (2006) Reciprocal interactions between adhesion receptor signaling and MMP regulation. Cancer Metastasis Rev 25:45–56CrossRefPubMedGoogle Scholar
  42. 42.
    Kwon GT, Cho HJ, Chung WY et al. (2009) Isoliquiritigenin inhibits migration and invasion of prostate cancer cells: possible mediation by decreased JNK/AP-1 signaling. J Nutr Biochem 20(9):663–676Google Scholar
  43. 43.
    Lim YC, Park HY, Hwang HS et al (2008) (−)-Epigallocatechin-3-gallate (EGCG) inhibits HGF-induced invasion and metastasis in hypopharyngeal carcinoma cells. Cancer Lett 271:140–152CrossRefPubMedGoogle Scholar
  44. 44.
    Van den Steen EP, Dubois B, Nelissen I et al (2002) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 37:375–536CrossRefPubMedGoogle Scholar
  45. 45.
    Takahra T, Smart DE, Oakley F et al (2004) Induction of myofibroblast MMP-9 transcription in three-dimensional collagen I gel cultures: regulation by NF-kappaB, AP-1 and Sp1. Int J Biochem Cell Biol 36:353–363CrossRefPubMedGoogle Scholar
  46. 46.
    Farina AR, Tacconelli A, Vacca A et al (1999) Transcriptional up-regulation of matrix metalloproteinase-9 expression during spontaneous epithelial to neuroblast phenotype conversion by SK-N-SH neuroblastoma cells, involved in enhanced invasivity, depends upon GT-box and nuclear factor kappa B elements. Cell Growth Differ 10:353–367PubMedGoogle Scholar
  47. 47.
    Sato H, Seiki M (1993) Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene 8:395–405PubMedGoogle Scholar
  48. 48.
    Taheri F, Bazan HE (2007) Platelet-activating factor overturns the transcriptional repressor disposition of Sp1 in the expression of MMP-9 in human corneal epithelial cells. Invest Ophthalmol Vis Sci 48:1931–1941CrossRefPubMedGoogle Scholar
  49. 49.
    Sato H, Kita M, Seiki M (1993) V-Src activates the expression of 92-kDa type IV collagenase gene through the AP-1 site and the GT box homologous to retinoblastoma control elements. J Biol Chem 268:23460–23468PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Gargi Maity
    • 1
  • Shabana Fahreen
    • 1
  • Aniruddha Banerji
    • 1
  • Paromita Roy Choudhury
    • 1
  • Triparna Sen
    • 1
  • Anindita Dutta
    • 1
  • Amitava Chatterjee
    • 1
  1. 1.Department of Receptor Biology and Tumor MetastasisChittaranjan National Cancer InstituteKolkataIndia

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