Isolation of a new cell population in the glioblastoma microenvironment

Abstract

Glioblastoma (GB) is a highly infiltrative tumor recurring in 90% of cases within a few centimeters of the resection cavity, even in cases of complete tumor resection and adjuvant chemo/radiotherapy. This observation highlights the importance of understanding this special zone of brain tissue surrounding the tumor. It is becoming clear that the nonneoplastic stromal compartment of most solid cancers plays an active role in tumor proliferation, invasion, and metastasis. Very little information, other than that concerning angiogenesis and immune cells, has been collected for stromal cells from GB. As part of a translational research program, we have isolated a new stromal cell population surrounding GB by computer-guided stereotaxic biopsies and primary culture. We named these cells GB-associated stromal cells (GASCs). GASCs are diploid, do not display the genomic alterations typical of GB cells, and have phenotypic and functional properties in common with the cancer-associated fibroblasts (CAFs) described in the stroma of carcinomas. In particular, GASCs express markers associated with CAFs such as fibroblast surface protein, alpha-smooth muscle actin (α-SMA), and platelet-derived growth factor receptor-beta (PDGFRβ). Furthermore, GASCs have a molecular expression profile different from that of control stromal cells derived from non-GB peripheral brain tissues. GASCs were also found to have tumor-promoting effects on glioma cells in vitro and in vivo. The isolation of GASCs in a tumor of neuroepithelial origin was unexpected, and further studies are required to determine their potential as a target for antiglioma treatment.

Suppression of SRC Signaling Is Effective in Reducing Synergy between Glioblastoma and Stromal Cells

“…In agreement, SRC-family inhibitor PP2 resulted similarly effective in modulating EGF-induced glioblastoma migration. The PDGF secreted by cancer cells has a dual role: directly sustains cancer cell survival and migration, but also determines (12). We have extended these observations demonstrating new properties of glioblastoma cells.…”

“…A fibroblast-like cell population was recently identified in computer-guided stereotaxic biopsies from glioblastoma surrounding tissue. These cells express CAFs associated markers, including fibroblast surface protein, alpha-smooth muscle actin (a-SMA), and b-PDGFR (12). The role of these cells in glioblastoma progression is under investigation.…”

Characterizing the peritumoral brain zone in glioblastoma: a multidisciplinary analysis

“…DNA index (DI) and the percentage of cell populations identified on the basis of different DNA contents were calculated with Modfit version 5.2 software (Verity Software House, Topsham, Maine) as previously described [15].…”

“…As part of the ''Grand Ouest Glioma Project'', funded by the French National Institute of Cancer, whose objective was to study tumor heterogeneity in GB [15][16][17][18][19][20][21][22], we performed a multidisciplinary analysis of the PBZ with a variety of techniques including radiology, histopathology, flow cytometry, omic analyses and primary cell cultures. The resulting PBZ profiles were compared with those of GB tumor zone (TZ) and normal brain samples to identify characteristics specific to the PBZ.…”

Glioblastoma angiogenesis: VEGF resistance solutions and new strategies based on molecular mechanisms of tumor vessel formation

“…Stromal cells-3: cancer-associated fibroblast. Glioblastoma-associated stromal cells which are diploid, do not have the genomic alterations typical of glioblastoma cells and have phenotypic and functional properties in common with the cancer-associated fibroblast described in the stroma of carcinomas have recently been isolated [27]. They expressed alpha-smooth muscle cell actin, suggesting a strong relationship with angiogenesis, a component of the vascular microenvironment, and a candidate for antiangiogenic treatment.…”