αv-Integrin isoform expression in primary human tumors and brain metastases

To determine whether metastasis to brain is associated with altered expression patterns of integrins, we investigated the expression of v3, v5, v6 and v8 integrins in primary malignancies and metastases to brain of breast, lung and renal carcinomas and in malignant melanoma. Inhibitors of v integrins are currently in clinical trials for glioblastoma. The role of integrins in the process of brain metastasis from other human tumors is unknown. Immunohistochemistry with novel integrin subtype specific rabbit monoclonal antibodies was performed on tissue microarrays of archival material of surgical biopsies taken from primary tumors and brain metastases. Integrin v3 expression was increased in brain metastases compared to primary tumors of breast adenocarcinoma, non-small cell lung cancer, renal clear cell cancer and malignant cutaneous melanoma (all p<0.01). Similarly, integrin v8 expression was increased in brain metastases compared to primary tumors of breast cancer (p<0.0001), lung cancer (p<0.01) and renal cancer (p<0.0001), with a similar trend in metastatic melanoma. Integrin v5 was expressed in most primary tumors (98% breast cancer; 67% lung cancer; 90% renal cancer; 89% melanoma) and showed a stronger expression in brain metastases compared to primary tumors from lung cancer and melanoma (p<0.05). Also integrin v6 expression was increased in brain metastases compared to primary breast cancer (p<0.001). Conclusions: The stronger v-integrin expression in brain metastases, especially of v3 and v8 integrins, suggests that certain v integrin are involved in the process of brain metastasis. v Integrins may be therapeutic targets for patients with metastatic cancer in brain. What's new? Cilengitide, a specific integrin-inhibitor is in a Phase III trial in glioblastoma. Anti-integrin agents might conceivably also be a therapeutic option for patients with brain metastasis. We investigated the expression of v3, v5, v6 and v8 integrins in various primary malignancies and metastases to brain. We found a significant stronger v-integrin expression in brain metastases. These v integrins could therefore be potential therapeutic targets for patients with brain metastasis. As cancer patients live longer due to improved primary tumor treatment, the prevalence of brain metastases has increased. Here the authors examined the promise of integrins, a family of cell surface glycoproteins involved in cell motility, attachment and invasion, as potential pharmacological targets in brain metastases. By comparing the expression levels of v3, v5, v6 and v8 integrins in various primary malignancies and metastases to the brain, they found a significantly stronger expression in brain metastases, especially of v3 and v8 integrins. Cilengitide, a specific integrin-inhibitor, is currently in late clinical trials for the treatment of glioblastoma, and the authors speculate that v integrins may also play specific pathogenetic functions in brain metastases that might be exploited therapeutically.