ITGAV targeting as a therapeutic approach for treatment of metastatic breast cancer

Am J Cancer Res. 2020 Jan 1;10(1):211-223. eCollection 2020.

Abstract

During tumorigenesis and metastasis, integrins regulate localization and activity of proteolytic enzymes that remodel the extracellular matrix. Previous studies have demonstrated blocking of αVβ3 to effectively inhibit proliferation, angiogenesis, and the survival of various cancer cell types. However, little is known about the functional role of the integrin subunit alpha-V gene (ITGAV) in metastatic breast cancer. In this study, ITGAV knockdown was used to identify the molecular mechanism by which ITGAV promotes tumorigenesis, metastasis, proliferation, invasion, and cellular self-renewal. The effectiveness of an ITGAV antagonist, cilengitide, for breast cancer treatment was investigated in vivo. Analysis of publicly available data demonstrated that overexpression of ITGAV was associated with poor relapse free survival of breast cancer patients. Silencing of ITGAV inhibited cell proliferation, invasion, and self-renewal of breast cancer cell lines by altering expression of BCL2 and PXN. The use of cilengitide significantly reduced lung metastasis in a metastatic breast cancer animal model. In conclusion, overexpression of ITGAV contributes to breast cancer metastasis through upregulation of PXN. Targeting ITGAV is a potential treatment for metastatic breast cancer as well as primary breast tumors with high ITGAV expression. ITGAV expression levels may be useful predictors of patient treatment and outcome responses.

Keywords: ITGAV; breast cancer; cilengitide; metastasis.