All-trans Retinoic Acid (ATRA), a Potential Inhibitor of Matrix Metalloproteinase-2 (MMP-2) and Tumour Invasion in Melanomas
Increased expression and activity of matrix metalloproteinase-2 (MMP-2) has been correlated with an increase in invasive potential and a worse prognosis in many cancers including melanomas. The antitumorigenic potential of all-trans retinoic acid (ATRA) in melanomas was studied using the highly metastatic murine melanoma cell line B16F10 as a model. Treatment of B16F10 cells with 20 µM/ml ATRA for 24 hrs caused a significant downregulation of MMP-2 expression and activity. Inhibition of MMP-2 activity appeared to be mediated via a significant decrease in expression of membrane type-1 matrix metalloproteinase (MT1-MMP), a crucial component of the MMP-2 activation complex, and extracellular matrix metalloproteinase inducer (EMMPRIN) and a significant increase in expression of tissue inhibitor of metalloproteinases-2 (TIMP-2). Downregulation of MMP-2 expression and activity would appreciably lower the invasive potential of melanoma cells. Inhibition of phosphorylation of focal adhesion kinase (FAK) upon ATRA treatment could inhibit intracellular signalling cascades and also downregulate MMP-2 levels and cell migration. The effectiveness of ATRA in inhibiting the migratory capabilities of B16F10 cells was confirmed by wound healing assay. Our findings thus elucidate important aspects about the molecular mechanisms of the effect of ATRA treatment on MMP-2 in melanomas and also indicate the anti-tumorigenic potential of ATRA which could have therapeutic value in clinical management of invasive melanomas.
Dr. Aniruddha Banerji
Post Graduate Department of Biotechnology, St. Xavier’s College (Autonomous), Kolkata, 30 Mother Teresa Sarani, Kolkata 700016, West Bengal, India.
Dr. Kirat Kumar Ganguly
Department of Microbiology, Michael Madhusudan Memorial College, Durgapur 713216, West Bengal, India.
Dr. Amitava Chatterjee
Faculty Centre of ‘Integrated Rural Development and Management’, Ramakrishna Mission Vivekananda Educational and Research Institute, Narendrapur, Kolkata 700103, West Bengal, India.
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