High Alpha V Integrin Level Of Cancer Cells Is Associated With Development Of Brain Metastasis In Athymic Rats

Background/Aim: Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an alpha v subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of alpha v integrin cell adhesion protein promoted metastatic phenotypes in cancer cells. Materials and Methods: Cancer cells from different origins were used and studied regarding their metastatic ability and intetumumab, anti-alpha v integrin mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases animal models. Results: The number of brain metastases and the rate of occurrence were positively correlated with cancer cell alpha v integrin levels. High alpha v integrin-expressing cancer cells showed significantly faster cell migration rate in vitro than low alpha v integrin-expressing cells. Intetumumab significantly inhibited cancer cell migration in vitro regardless of alpha v integrin expression level. Overexpression of alpha v integrin in cancer cells with low alpha v integrin level accelerated cell migration in vitro and increased the occurrence of brain metastases in vivo. Conclusion: alpha v integrin promotes brain metastases in cancer cells and may mediate early steps in the metastatic cascade, such as adhesion to brain vasculature. Targeting alpha v integrin with intetumumab could provide clinical benefit in treating cancer patients who develop metastases.