Department of Biosciences and Biotechnology, University of Milan Bicocca, Piazza della Scienza 2, Building U3, 20126 Milan, Italy.
J Mol Med (Berl). 2009 Nov;87(11):1087-95. doi: 10.1007/s00109-009-0535-3. Epub 2009 Sep 29.
Cancers comprise heterogeneous cells, ranging from highly proliferative immature precursors to more differentiated cell lineages. In the last decade, several groups have demonstrated the existence of cancer stem cells in both nonsolid solid tumors, including some of the brain: glioblastoma multiforme (GBM), medulloblastoma, and ependymoma. These cells, like their normal counterpart in homologous tissues, are multipotent, undifferentiated, self-sustaining, yet transformed cells. In particular, glioblastoma-stem like cells (GBSCs) self-renew under clonal conditions and differentiate into neuron- and glia-like cells, with aberrant, mixed neuronal/astroglial phenotypes. Remarkably, upon subcutaneous and intracerebral transplantation in immunosuppressed mice, GBSCs are able to form secondary tumors that closely resemble the human pathology, a property retained also throughout serial transplantation. The search is up for the identification of the markers and the molecular mechanisms that underpin the tumorigenic potential of these cells. This is critical if we aim at defining new therapeutic approaches for the treatment of malignant brain tumors. Lately, it has been shown that some key regulatory system that plays pivotal roles in neural stem cell physiology can also regulate the tumorigenic ability of cancer stem cells in GBMs. This suggests that the study of cancer stem cells in brain tumors might help to identify new and more specific therapeutic molecular effectors, with the cancer stem cells themselves representing one of the main targets, in fact the Holy Grail, in cancer cell therapy. This review includes a summary review on brain cancer cells and their usefulness as emerging targets in cancer cell therapy.
癌症由异质性细胞组成,范围从高度增殖的不成熟前体细胞到更分化的细胞谱系。在过去的十年中,有几个小组已经证明了癌症干细胞在包括大脑在内的实体肿瘤中的存在:多形性胶质母细胞瘤(GBM)、髓母细胞瘤和室管膜瘤。这些细胞与同源组织中的正常细胞一样,具有多能性、未分化性、自我维持性,但具有转化性。特别是,胶质母细胞瘤样细胞(GBSCs)在克隆条件下自我更新,并分化为神经元和神经胶质样细胞,具有异常的、混合的神经元/星形胶质细胞表型。值得注意的是,在免疫抑制小鼠的皮下和脑内移植后,GBSCs 能够形成与人类病理非常相似的次级肿瘤,这种特性在连续移植中也得以保留。人们正在寻找鉴定这些细胞的标志物和分子机制,这些标志物和分子机制是这些细胞肿瘤发生潜力的基础。如果我们旨在确定治疗恶性脑肿瘤的新治疗方法,这一点至关重要。最近已经表明,在神经干细胞生理学中发挥关键作用的一些关键调节系统也可以调节 GBM 中癌症干细胞的肿瘤发生能力。这表明研究脑肿瘤中的癌症干细胞可能有助于确定新的、更特异的治疗性分子效应物,而癌症干细胞本身就是癌症细胞治疗的主要靶点之一,实际上是圣杯。这篇综述包括对脑癌细胞及其作为癌症细胞治疗中新兴靶点的有用性的综述。