Abstract
Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion. IQGAP1 has been identified as a marker of amplifying cancer cells in GBMs. To determine the involvement of IQGAP1 in the onco-biology of GBM, we performed immunohistochemical confocal microscopic analysis of the IQGAP1 protein in human GBM tissue samples using cell type-specific markers. IQGAP1 immunostaining and subcellular localization was heterogeneous; the protein was located in the plasma membrane and, at variable levels, in nucleus and/or cytosol. Moreover, IQGAP1 positive staining was found in podosome/invadopodia-like structures. IQGAP1+ staining was observed in neurons (Map2+ cells), in cancer stem cells (CSC; nestin+) and in several macrophages (CD31+ or Iba1+). Our results indicate that the IQGAP1 protein is involved in normal cell physiology as well as oncologic processes.
Highlights
Glioblastoma multiforme (GBM) is the most frequent and aggressive of all primary brain tumors, characterized by poor outcomes; after surgery and radiotherapy, the median survival of patients is less than one year; the overall survival (OS) at two years is less than 10%; and the OS at five years is less than 2% [1,2,3]
We show evidence of IQGAP1 involvement in GBM onco-biology, including glioma-infiltrating myeloid cells (GIMs), remaining neurons, endothelial vascular cells, and astrocytes
IQGAP1 immunoreactivity in GBM tissue sections exhibited a variable pattern of expression, depending on the origin of tumor, area of tumor and even in specific astrocytes within the same tumor
Summary
Glioblastoma multiforme (GBM) is the most frequent and aggressive of all primary brain tumors, characterized by poor outcomes; after surgery and radiotherapy, the median survival of patients is less than one year; the overall survival (OS) at two years is less than 10%; and the OS at five years is less than 2% [1,2,3]. IQGAP1 connects elements of the cytoskeleton to cell adhesion and some signaling molecules and modulates cell morphology, motility, cell cycle and other cellular functions [8,9], always facilitating and coordinating the spatiotemporal organization and the sequential activation of structural and signaling molecules [10,11]. Because of this association with molecular partners, IQGAP1 contributes to cell fate, polarization, tumorigenesis, migration, tumor progression and angiogenesis [12,13]. Anti-GFAP Anti-Iba Anti-PCNA Anti-Nestin Anti-CD31 Anti-Map Anti-β-tubulin Phalloidin-TRITC
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