Laboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Cancer Res. 2011 Feb 1;71(3):634-9. doi: 10.1158/0008-5472.CAN-10-3220. Epub 2011 Jan 25.
Tumors are being increasingly perceived as abnormal organs that, in many respects, recapitulate the outgrowth and differentiation patterns of normal tissues. In line with this idea is the observation that only a small fraction of tumor cells is capable of initiating a new tumor. Because of the features that these cells share with somatic stem cells, they have been termed cancer stem cells (CSC). Normal stem cells reside in a "stem cell niche" that maintains them in a stem-like state. Recent data suggest that CSCs also rely on a similar niche, dubbed the "CSC niche," which controls their self-renewal and differentiation. Moreover, CSCs can be generated by the microenvironment through induction of CSC features in more differentiated tumor cells. In addition to a role in CSC maintenance, the microenvironment is hypothesized to be involved in metastasis by induction of the epithelial-mesenchymal transition, leading to dissemination and invasion of tumor cells. The localization of secondary tumors also seems to be orchestrated by the microenvironment, which is suggested to form a premetastatic niche. Thus, the microenvironment seems to be of crucial importance for primary tumor growth as well as metastasis formation. Combined with its role in the protection of CSCs against genotoxic insults, these data strongly put forward the niche as an important target for novel therapies.
肿瘤正逐渐被视为异常器官，在许多方面，它们再现了正常组织的生长和分化模式。与这一观点一致的是，只有一小部分肿瘤细胞能够引发新的肿瘤。由于这些细胞与体干细胞具有共同特征，因此被称为癌症干细胞（CSC）。正常干细胞存在于“干细胞龛位”中，使其保持在干细胞样状态。最近的数据表明，CSC 也依赖于类似的龛位，称为“CSC 龛位”，控制其自我更新和分化。此外，CSC 可以通过诱导更分化的肿瘤细胞中的 CSC 特征，由微环境产生。除了在 CSC 维持中的作用外，微环境还被假设通过诱导上皮-间充质转化参与转移，导致肿瘤细胞的扩散和侵袭。继发性肿瘤的定位似乎也由微环境协调，这表明微环境形成了一个前转移龛位。因此，微环境似乎对原发性肿瘤生长和转移形成都至关重要。结合其在保护 CSC 免受遗传毒性损伤方面的作用，这些数据强烈地将龛位作为新疗法的一个重要靶点。
