The Association of Integrins beta 3, beta 4, and alpha V beta 5 on Exosomes, CTCs and Tumor Cells with Localization of Distant Metastasis in Breast Cancer Patients

Integrins are cell adhesion receptors, which play a role in breast cancer invasion, angiogenesis, and metastasis. Moreover, it has been shown that exosomal integrins provide organotropic metastasis in a mouse model. In our study, we aimed to investigate the expression of integrins beta 3, beta 4, and alpha V beta 5 on exosomes and tumor cells (circulating tumor cells and primary tumor) and their association with the localization of distant metastasis. We confirmed the association of exosomal integrin beta 4 with lung metastasis in breast cancer patients. However, we were unable to evaluate the role of integrin beta 3 in brain metastasis due to the rarity of this localization. We established no association of exosomal integrin alpha V beta 5 with liver metastasis in our cohort of breast cancer patients. The further evaluation of beta 3, beta 4, and alpha V beta 5 integrin expression on CTCs revealed an association of integrin beta 4 and alpha V beta 5 with liver, but not the lung metastases. Integrin beta 4 in the primary tumor was associated with liver metastasis. Furthermore, an in-depth analysis of phenotypic characteristics of beta 4+ tumor cells revealed a significantly increased proportion of E-cadherin+ and CD44+CD24- cells in patients with liver metastases compared to patients with lung or no distant metastases.