Resumen de Expression of integrins ?vß3 and ?vß5 and their ligands in primary and secondary central nervous system neoplasms

Michel Mittelbronn, Arne Warth, R. Meyermann, Simon Goodman, Michael Weller

• Aims: To study the expression of integrins ?vß3 and ?vß5 and their ligands in tumour, stroma and endothelial cells from human glioblastoma and CNS metastases from breast, lung and skin tumours. Methods and results: Integrin and integrin ligand expression was quantified in frozen tumour surgical specimens (15 glioblastomas and breast carcinoma metastases as well as 16 lung carcinoma and melanoma metastases) using immunohistochemistry. Gene expression profiles were evaluated in glioblastomas (n=424) and in normal brain (n=11). Overall, ?vß3 expression was more common than ?vß5, except in tumours derived from lung. ?vß3 expression was most frequent in glioblastomas and melanoma metastases. Most lung-derived tumours expressed ?vß5, but expression was less frequent in other tumours; about 20% of breast-derived tumours strongly expressed ?vß5. Melanoma-derived tumours did not express ?vß5. Expression of integrin ligands vitronectin, fibrinogen, fibronectin and osteopontin was variable between tumours, although most tumours expressed the ligands to some extent. Marked ?vß3, but not ?vß5, expression was common in stroma of CNS metastases. In blood vessels, ?vß3 expression was more frequent than ?vß5 and more pronounced in CNS metastases than in glioblastomas. Integrin ligand expression occurred in blood vessels in most tumours. In glioblastomas, mRNA expression of ?vß3, ?vß5, osteopontin and fibronectin were significantly upregulated over normal brain. Conclusions: Overall, we report distinct and heterogeneous patterns of integrin expression in primary and secondary brain tumours that may be relevant to the future development of integrin-targeting therapeutic approaches to brain tumours.