Expression of integrins αvβ3 and αvβ5 and their ligands in primary and secondary central nervous system neoplasms

Abstract

Aims: To study the expression of integrins αvβ3 and αvβ5 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, αvβ3 expression was more common than αvβ5 except in tumours derived from lung. αvβ3 expression was most frequent in glioblastomas and melanoma metastases. Most lung-derived tumours expressed αvβ5 but expression was less frequent in other tumours; about 20% of breast-derived tumours strongly expressed αvβ5. Melanoma-derived tumours did not express αvβ5. Expression of integrin ligands vitronectin, fibrinogen, fibronectin and osteopontin was variable between tumours, although most tumours expressed the ligands to some extent. Marked αvβ3, but not αvβ5, expression was common in stroma of CNS metastases. In blood vessels, αvβ3 expression was more frequent than αvβ5 and more pronounced in CNS metastases than in glioblastomas. Integrin ligand expression occurred in blood vessels in most tumours. In glioblastomas, mRNA expression of αvβ3, αvβ5, 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.