Beyond cell adhesion: Vitronectin regulates tumor growth

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A lot is known about extracellular matrix protein vitronectin. Its structure, composed of three main domains, and its direct implication in vitronectin’s cellular function, has been studied in extensive detail for a long time. We know vitronectin, like fibronectin, is a key protein of the ECM with important roles in wound healing (Koivisto et al.; Advances in Wound Care; 2013). Which is why new studies implicating vitronectin in novel functions are fascinating to come across.

One such study in question, published by the lab of Nicolai Sidenius at the European Institute of Oncology’s IFOM-IEO research institute in the journal Blood (Pirazzoli et al.; Blood; 2013, 121:2316), presents evidence of vitronectin’s direct influence on tumor growth and recession and confirms vitronectin as an interesting drug target.

It has been known for some time that vitronectin’s Somatomedin B domain interacts with the urokinase plasminogen activator receptor (uPAR) (Gardsvoll and Ploug; J Biol Chem.; 2007 282(18):13561-72). By preparing mutants of uPAR incapable of binding vitronectin and both vitronectin and uPA, the authors demonstrated that cells with these mutants, which lack wild type uPAR function, lacked cell adhesion, spreading, migration, and proliferation function. The authors then followed findings with in vivo studies in severe combined immunodeficiency mice. And the findings were fascinating: In vivo, they showed that the uPAR mutant incapable of binding vitronectin resulted in strongly reduced tumor formation. This is a remarkable finding that directly relates the interaction between uPAR and vitronectin to tumor growth.

Previously, the vitronectin family of integrins, key components of the extracellular matrix, had been identified as interesting drug targets, due to their direct involvement in cell survival upon tumor invasion (Murphy and Stupack; Cell-Extracellular Matrix Interactions in Cancer; 2010, 137-170). This is beyond its well-known function in wound healing and viral infection.

This is interesting to us, because, as a supplier of vitronectin, we work with researchers to provide pure, biologically active human plasma-derived vitronectin to aid biomedical research and further such discoveries. Contact us to enquire about our vitronectin grades and our bioassay development capabilities, and find out how we can help move your research.

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