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Culture of human breast cancer cell line (MDA-MB-231) on fibronectin-coated surface induces pro-matrix metalloproteinase-9 expression and activity

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Tumor Biology

Abstract

Interaction between cell surface integrin receptors with extracellular matrix (ECM) plays an important role in cell survival, proliferation, and migration including tumor development and invasion. Binding of ECM to integrins initiates intracellular signaling cascades, modulating expression and activity of different matrix metalloproteinases (MMPs) which is important in ECM degradation. The present study investigates fibronectin–integrin-mediated signaling and thereby modulation of MMPs expression and activity in human breast cancer cell line, MDA-MB-231. Culture of MDA-MB-231 cells on fibronectin (FN) induced expression and activity of pro-matrixmetalloproteinase-9 (MMP-9). Appreciable reduction of FN-induced pro-MMP-9 activity was observed in anti-α5 antibody treated cells. Inhibitor studies revealed that inhibitors of phosphatidyl inositiol-3-kinase (PI-3K), and nuclear factor kappa B (NF-κB) inhibited FN-induced pro-MMP-9 activity. FN increased tyrosine phosphorylation of focal adhesion kinase (FAK), integrin linked kinase (ILK), and PI-3K in MDA-MB-231 cells. FN-induced the transactivation of MMP-9 promoter by enhancing DNA binding activity of NF-κB and Sp1. Wound healing assay showed faster migration of MDA-MB-231cells grown on fibronectin-coated as surface as compared to control. Our findings indicated that culture of MDA-MB-231 on fibronectin perhaps send signals via fibronectin–integrin-mediated signaling pathways recruiting FAK, PI-3K, ILK, NF-κB, and modulate expression and activation of pro-MMP-9. These observations may enrich fundamental aspects of cancer biology especially role of α5β1 integrin in regulation of MMPs expression and activity.

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Acknowledgments

We acknowledge the Director of the Chittaranjan National Cancer Institute for Institute facilities and financial support, and the Indian Council for Medical Research (ICMR), New Delhi, India (Grant No. 5/13/49/05/NCD-III) for financial support.

Conflicts of interest

All authors hereby disclose that they do not have any financial and/or personal relationships with other people of organization that could in appropriately influence (bias) their work. The authors declare that “there are no conflicts of interest”.

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Authors and Affiliations

  1. Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata, 700026, West Bengal, India

    Gargi Maity, Paromita Roy Choudhury, Triparna Sen, Kirat Kumar Ganguly, Hrishikesh Sil & Amitava Chatterjee

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  1. Gargi Maity
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  2. Paromita Roy Choudhury
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  3. Triparna Sen
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  4. Kirat Kumar Ganguly
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  6. Amitava Chatterjee
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Corresponding author

Correspondence to Amitava Chatterjee.

Additional information

Gargi Maity and Paromita Roy Choudhury contributed equally to the studies presented in the manuscript.

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Maity, G., Choudhury, P.R., Sen, T. et al. Culture of human breast cancer cell line (MDA-MB-231) on fibronectin-coated surface induces pro-matrix metalloproteinase-9 expression and activity. Tumor Biol. 32, 129–138 (2011). https://doi.org/10.1007/s13277-010-0106-9

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  • DOI: https://doi.org/10.1007/s13277-010-0106-9

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