Abstract C56: High αV integrin level is associated with metastasis to the brain in athymic rat hematogenous models

Abstract

Abstract Brain metastases from systemic cancers occur in approximately 20% of lung cancer patients including both small cell lung carcinoma (SCLC) and non–small-cell lung cancer (NSCLC), and in 5-8% of breast cancer and melanoma. Brain metastases tend to present as multiple brain lesions with high morbidity and poor prognosis. We investigated the expression of αV integrin cell adhesion protein in multiple human cancer cell lines (3 SCLC, 4 NSCLC, 2 melanoma, 1 breast cancer), and its correlation with migration in vitro and brain metastatic ability in vivo using a hematogenous metastasis technique in which cancer cells are infused into the internal carotid artery in athymic nude rats. Expression of αV integrin protein was highly variable among human cancer cell lines. Four cell lines tested had high αV integrin expression and formed multiple brain metastases. H460 NSCLC cells formed 13 ± 6 metastases per brain (mean volume 3 ± 9 mm3) with median survival 34 days (n = 4). A549 lung adenocarcinoma cells formed 9 ± 5 metastases per brain (8 ± 21 mm3 volume, 62 day survival, n = 6). MDA-MB231BR-HER2 breast cancer and A2058 melanoma cells also formed multiple brain metastases. Low αV expressing lung cancer cells, including H146 and DMS79 SCLC, and H520 squamous NSCLC cells failed to form brain metastases by 12-16 weeks after intracarotid cell infusion. In an in vitro gap closure migration assay, A549 cells (high αV integrin) showed a higher rate of migration than H520 cells (low αV integrin). Regardless of αV integrin level, incubation with intetumumab anti-αV integrin monoclonal antibody significantly inhibited cell migration of both A549 and H520 cells. We conclude that cancer cellular αV integrin level is positively correlated to the development of brain metastases and may be a potential biomarker of patients likely to develop brain metastases. We suggest that blocking αV integrin with intetumumab has prophylactic potential to prevent distant metastasis and improve survival in cancer patients. Citation Format: Jeffrey Wu, Michael Pagel, Leslie L. Muldoon, Edward A. Neuwelt. High αV integrin level is associated with metastasis to the brain in athymic rat hematogenous models. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr C56.