The brain tumor microenvironment

Abstract

High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumors cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells may be the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells-such as vascular cells, microglia, peripheral immune cells, and neural precursor cells-also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact and signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural stem and progenitor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. © 2011 Wiley-Liss, Inc.

IQGAP1 in Podosomes/Invadosomes Is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

“…The proinflammatory phenotype of the GBM associated microglial cell seems to be suppressed within the GBM environment becoming a cell that promotes glioma cell migration, neither oligodendrocytes nor endothelial cells promoted the migration and the effects of macrophages from the periphery on glioma growth are different from those of microglia [38]. TAMs were mainly located in the marginal area (Supplementary Materials, Figure S2), close to nestin + GSCs and both around microvessels CD31 + endothelial cells (Figure 2F-O) confirming data reported by Ye et al [40].…”

“…Figure 7 is a simplified model of some of the proteins involved in the podosome/invadopodia generation mechanism and a model of the involvement of IQGAP1 in GBM progression based on the present study. Figure 7 also includes IQGAP1 relations with the upstream signaling pathway involving the small GTP-binding proteins Cdc42/Rac1 and Arp2/3-N-WASp interacting complexes [38,47,49]. …”

IQGAP1 in Podosome /Invadosome is Involved in the Progression of Glioblastoma Multiforme Depending on the Tumor Status

“…The proinflammatory phenotype of the GBM associated microglial cell seems to be suppressed within the GBM environment becoming a cell that promotes glioma cell migration, neither oligodendrocytes nor endothelial cells promoted the migration and the effects of macrophages from the periphery on glioma growth are different from those of microglia [38]. TAMs were mainly located in the marginal area (Supplemental Figure S2), close to nestin + GSCs and both around microvessels CD31 + endothelial cells ( Figure 2F-O) confirming data reported by Ye et al [40].…”

Standard of care therapy for malignant glioma and its effect on tumor and stromal cells

“…There are several cell types that make up the tumor stroma and can contribute to the biology of glioma to include astrocytes, endothelial cells, pericytes and cells involved in the immune response (that is, microglia and T-lymphocytes; Daginakatte and Gutmann, 2007;Charles et al, 2011). The tumor microenvironment is enriched with soluble factors secreted by these cells.…”

“…The relevance of the tumor stroma to glioma maintenance has recently gained a great deal of attention and the various cell types that contribute to the tumor stroma have been implicated in producing products that support the proliferation and migration of glioma cells (Charles et al, 2011). One intriguing possibility is that tumor stromal cells or their products may be reasonable therapeutic targets in the management of this disease.…”