TITLE:
Integrin Alpha-V Beta-3-Matrix Metalloproteinase-2 (MMP-2), Cross-Talk
AUTHORS:
Hrishikesh Sil, Amitava Chatterjee
KEYWORDS:
Breast Cancer, MMP-2, Alpha V Beta3, MT1-MMP, TIMP-2, EMPRIN, VEGF
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.6 No.9,
August
28,
2015
ABSTRACT: The present study aimed to detect comparative expression of integrin αVβ3 and its involvement in expression and activation of matrix
metalloproteinase-2 (MMP-2) in 25 malignant human breast tumor and adjacent normal
breast tissues from different clinical TNM stages (DCIS to T4) of the disease and
possible involvement of known regulating parameters of MMP-2 like TIMP-2, MT1-MMP
and EMPRIN. Integrin αVβ3 was highly expressed in tumors
than adjacent normal breast tissues. Pro-MMP-2(72-KD) was mainly expressed in adjacent
normal tissues compared to tumors. The mature forms of MMP-2 (68 KD and 64 KD) were
found only in tumors. Appreciable expression of TIMP-2 and induction of MT1-MMP
and EMPRIN in T2-T4 stages suggested their possible role in MMP-2 activation. Over
expression Integrin αVβ3 in tumors than adjacent normal breast
tissues was an indication of cancer progression with involvement of integrin signaling.
We conclude that, the co-precipitation of MMP-2 with αvβ3 by anti-αv antibody is a strong
indication that integrin αvβ3 is a surface receptor for MMP-2
and αvβ3-MMP-2 complex on the surface of tumor cells may play a
very important role in determining the invasive property and malignant behavior
of tumor tissues. The positive expression of endogenous inhibitor of MMP-2, TIMP-2
may have an appreciable role in activation of this protease and risk of malignancy
in advanced stage of the disease. The enhanced expression of MT1-MMP and EMPRIN
suggested a role for these factors in gelatinase regulation. However the exact mechanism(s)
remains to be investigated. Finally, evaluation of integrin αVβ3 associated MMP-2 expression and activity may add valuable
information and can possibly be therapeutic target. The clinical exploitation of
integrins will provide oncologists with novel therapeutic strategies for the treatment
of malignancy in breast cancer.