Periostin is Secreted by Glioblastoma CD90-positive Stromal Cells and Acts as a Pericyte Chemoattractant

Abstract

Glioblastoma (GBM) stroma is composed of multiple cell types including vascular elements, immune cells and mesenchymal stromal cells (MSCs). Periostin (POSTN) is a secreted extracellular matrix protein which plays a crucial role in the progression of this aggressive and highly vascularized tumor. However, the cellular distribution of gliomaderived POSTN and whether POSTN can act as a chemoattractant for tumor vasculogenic cells is not known. The aim of the present study was to identify the specific cellular distribution of POSTN within GBM and to explore the possibility of POSTN acting as an attractant for tumor pericytes. Here we show that POSTN expression by large is restricted to the stromal compartment of GL261 mouse GBM. Within the stroma, POSTN is mainly localized to CD90+, most likely mesenchymal stromal cells (MSCs), and to pericytes recruited into the tumor. High POSTN protein levels were found to be produced by CD90+ MSCs acutely isolated from human GBM. Both mouse and human CD90+ MSCs co-expressed POSTN and Integrin β1, permitting autocrine interaction between ligand and receptor. Pericytes expressing Integrin β1 and CD90+ perivascular cells expressing POSTN are adjacently localized within the mouse GL261 stroma. A large fraction of human brain pericytes were found to express Integrin β1 and showed Integrin β1- dependent migration in response to POSTN. In summary, our findings tie the expression and action of POSTN to the stromal compartment of GBM and support a role for POSTN in GBM angioproliferation.