Rotoli Deborah, Pérez-Rodríguez Natalia Dolores, Morales Manuel, Maeso María Del Carmen, Ávila Julio, Mobasheri Ali, Martín-Vasallo Pablo
Laboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular and Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, La Laguna, Av. Astrofísico Sánchez s/n, 38206 La Laguna, Tenerife, Spain.
CNR-National Research Council, Institute of Endocrinology and Experimental Oncology (IEOS), Via Sergio Pansini, 5-80131 Naples, Italy.
Int J Mol Sci. 2017 Jan 13;18(1):150. doi: 10.3390/ijms18010150.
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.
多形性胶质母细胞瘤（GBM）是最常见且侵袭性最强的原发性脑肿瘤。GBM由非常异质性的星形胶质细胞群体、神经元、新生血管以及浸润性髓样细胞（小胶质细胞和单核细胞衍生的巨噬细胞）构成。IQGAP1支架蛋白与细胞骨架成分、细胞粘附分子以及多种信号分子相互作用，以调节细胞形态和运动性、细胞周期及其他细胞功能。在多种肿瘤中均观察到IQGAP1的过表达和异位定位，提示该蛋白在细胞增殖、转化和侵袭中发挥作用。IQGAP1已被确定为GBM中扩增癌细胞的标志物。为了确定IQGAP1在GBM肿瘤生物学中的作用，我们使用细胞类型特异性标志物对人GBM组织样本中的IQGAP1蛋白进行了免疫组织化学共聚焦显微镜分析。IQGAP1的免疫染色和亚细胞定位是异质性的；该蛋白位于质膜，且在细胞核和/或细胞质中存在不同程度的表达。此外，在足体/侵袭性伪足样结构中发现了IQGAP1阳性染色。在神经元（Map2⁺细胞）、癌症干细胞（CSC；巢蛋白⁺）以及多种巨噬细胞（CD31⁺或Iba1⁺）中观察到了IQGAP1⁺染色。我们的结果表明，IQGAP1蛋白参与正常细胞生理以及肿瘤学过程。
