Fibulin-3 is uniquely upregulated in malignant gliomas and promotes tumor cell motility and invasion.

摘要: Malignant gliomas are highly invasive tumors with an almost invariably rapid and lethal outcome. Surgery chemoradiotherapy fail to remove resistant tumor cells that disperse within normal tissue, which a major cause for disease progression therapy failure. Infiltration of the neural parenchyma is distinctive property malignant compared other solid tumors. Thus, glioma thought produce unique molecular changes remodel extracellular matrix form microenvironment permissive their motility. Here, we describe expression proinvasive role fibulin-3, mesenchymal protein specifically upregulated in gliomas. Fibulin-3 downregulated peripheral inhibit growth. However, found fibulin-3 cultured cells, although was undetectable brain or astrocytes. Overexpression knockdown experiments revealed did not seem affect cell morphology proliferation, but enhanced substrate-specific adhesion promoted motility dispersion organotypic cultures. Moreover, orthotopic implantation fibulin-3-overexpressing resulted diffuse increased volume rostrocaudal extension controls. Tumors overexpressing also showed elevated activity metalloproteases, such as MMP-2/MMP-9 ADAMTS-5. Taken together, our results suggest has protumoral gliomas, could be potential target against progression. Strategies this glioma-specific component disrupt mechanisms restrict dissemination these