National Institute for Cancer Research (IST), IRCCS, and Department of Oncology Biology and Genetics (DOBIG), University of Genoa, Genoa, Italy.
Brain Pathol. 2010 May;20(3):527-38. doi: 10.1111/j.1750-3639.2009.00335.x. Epub 2009 Sep 25.
Gliomas are aggressive and almost incurable glial brain tumors which frequently display abnormal platelet-derived growth factor (PDGF) signaling. Evidence gained from studies on several in vivo animal models has firmly established a causal connection between aberrant PDGF signaling and the formation of some gliomas. However, only recently has significant knowledge been gained regarding crucial issues such as the glioma cell of origin and the relationship between the transforming stimulus and the cellular characteristics of the resulting tumor. Based on recent evidence, we propose that PDGF can bias cell-fate decisions, driving the acquisition of cell type-specific features by the progeny of multipotent neural progenitors, thus determining the shape and direction of the transformation path. Furthermore, recent data about the cellular mechanisms of PDGF-driven glioma progression and maintenance indicate that PDGF may be required, unexpectedly, to override cell contact inhibition and promote glioma cell infiltration rather than to stimulate cell proliferation.
神经胶质瘤是一种侵袭性且几乎无法治愈的神经胶质脑肿瘤,其常表现出异常的血小板衍生生长因子(PDGF)信号。在几个体内动物模型研究中获得的证据,已明确确定了异常的 PDGF 信号与某些神经胶质瘤形成之间的因果关系。然而,直到最近,人们才对一些关键问题有了更深入的了解,如神经胶质瘤的起源细胞以及转化刺激与肿瘤细胞特征之间的关系。基于最近的证据,我们提出 PDGF 可以影响细胞命运决定,使多能神经祖细胞的后代获得特定细胞类型的特征,从而决定转化途径的形状和方向。此外,最近关于 PDGF 驱动神经胶质瘤进展和维持的细胞机制的数据表明,PDGF 可能出乎意料地需要克服细胞接触抑制并促进神经胶质瘤细胞浸润,而不是刺激细胞增殖。