Journal of Environmental Pathology, Toxicology and Oncology

ISSN for PRINT: 0731-8898

For Online Access

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2001, Volume20

Issue 3

90 pages

Issue price - $160.00

Amitava Chatterjee
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata-700 026, India

Nibedita Chattopadhyay
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Calcutta, India

One of the most important cell surface receptors in tumor development is avb3. To study the role of the avb3 integrin receptor in the invasive properties of tumor cells, we used human cervical tumor cells SiHa (cell surface avb3 integrin receptor-positive) and HeLa cells (cell surface avb3 integrin receptor-negative). Cell adhesion assay showed that SiHa and HeLa cells can bind very efficiently to extracellular matrix proteins fibronectin, laminin, and collagen IV, but the binding of HeLa cells to vitronectin is very poor compared to that of SiHa cells. Comparative invasion assay demonstrated a much lower invasive potential of HeLa cells than SiHa cells. Cell surface av and b3 integrin receptor subunit assay showed the expression of avb3 integrin receptor on the SiHa cell surface, whereas the HeLa cell surface lacks functional avb3 heterodimer. The zymo-gram demonstrated a higher gelatinase/MMP-2 activity in culture medium, whole cell, and membrane extract of SiHa cells than that in HeLa cells. The avb3 integrin receptor-associated MMP-2 activity of SiHa and HeLa cells was tested in a comparative zymography that clearly showed very high gelatinase/MMP-2 activity in av mAb-immunoprecipitated fraction of SiHa cell (containing avb3 heterodimer) but not in the av mAb-immunoprecipitated fraction of HeLa cell membrane extract (containing only the b3 subunit). Immu-noblot assay of av monoclonal antibody-immunoprecipitated avb3 integrin receptor from SiHa cell membrane extract with MMP-2 monoclonal antibody demonstrated the association of MMP-2 protein with avb3 integrin receptor. We concluded that avb3 integrin receptor is one of the most important cell surface molecules regulating the invasive property of cervical tumor cells because of its associated gelatinase/MMP-2 activity. Our findings will contribute to a better understanding of the role of integrin receptors, especially of the avb3 integrin receptor, in the invasive property of cancer cells and possibly affect future therapeutic approaches to cancer invasion and metastasis.

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