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Journal of Cancer Research and Clinical Oncology

, Volume 137, Issue 2, pp 347–357 | Cite as

Laminin induces matrix metalloproteinase-9 expression and activation in human cervical cancer cell line (SiHa)

  • Gargi Maity
  • Triparna Sen
  • Amitava Chatterjee
Original Paper

Abstract

Purpose

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. Matrix metalloproteinases (MMP) are a family of metalloproteinases capable of digesting ECM and facilitate cell migration. Binding of ECM to integrins initiates signaling cascades modulating expression and activity of different MMPs. The present study investigates whether laminin-mediated signaling modulates matrix metalloproteinases (MMP) expression and activity in human cervical cancer cell (SiHa).

Methods

Western blot, immunocytochemistry, ELISA, zymography, RT–PCR, EMSA and wound-healing assay were used.

Results

Culture of SiHa cells on laminin (LN)-coated surface induces MMP-9 expression and activation. Wound-healing assay showed that SiHa cells migrate much faster on laminin-coated surface than that of control. LN-induced MMP-9 expression and activation was appreciably reduced with treatment of extracellular signal–regulated kinase (ERK) inhibitor, phosphatidylinositol-3-kinase (PI-3K) inhibitor and anti-α2 antibody. Phosphorylation of focal adhesion kinase (FAK), ERK, and PI-3K was increased upon LN stimulation. LN induces nuclear translocation of PI-3K and nuclear factor kappa B (NF-κB). LN increases DNA-binding activity of NF-κB and activator protein-1 (AP-1) to MMP-9 promoter.

Conclusions

Our findings indicate laminin-induced MMP-9 expression and activation possibly via α2β1 integrin-mediated signaling involving FAK, PI-3K, ERK followed by transcriptional upregulation of MMP-9.

Keywords

Laminin Integrin MMP-9 ERK PI-3K NF-κB 

Notes

Acknowledgments

We acknowledge Director, Chittaranjan National Cancer Institute for Institute facilities, financial support and Department of Science and Technology, New Delhi (Grant No. SR/SO/HS-59/2004) for financial support.

Conflict of interest statement

None.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Receptor Biology and Tumor MetastasisChittaranjan National Cancer InstituteKolkataIndia

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