Department of Stem Cell Biology and Regenerative Medicine, Cleveland Clinic, Cleveland, OH 44195, USA.
Cell Stem Cell. 2010 May 7;6(5):421-32. doi: 10.1016/j.stem.2010.02.018.
Cancer stem cells (CSCs) are a subpopulation of tumor cells suggested to be critical for tumor maintenance, metastasis, and therapeutic resistance. Prospective identification and targeting of CSCs are therefore priorities for the development of novel therapeutic paradigms. Although CSC enrichment has been achieved with cell surface proteins including CD133 (Prominin-1), the roles of current CSC markers in tumor maintenance remain unclear. We examined the glioblastoma stem cell (GSC) perivascular microenvironment in patient specimens to identify enrichment markers with a functional significance and identified integrin alpha6 as a candidate. Integrin alpha6 is coexpressed with conventional GSC markers and enriches for GSCs. Targeting integrin alpha6 in GSCs inhibits self-renewal, proliferation, and tumor formation capacity. Our results provide evidence that GSCs express high levels of integrin alpha6, which can serve not only as an enrichment marker but also as a promising antiglioblastoma therapy.
癌症干细胞(CSC)是肿瘤细胞的一个亚群,被认为对肿瘤的维持、转移和治疗耐药至关重要。因此,前瞻性地识别和靶向 CSC 是开发新的治疗模式的优先事项。尽管已经通过细胞表面蛋白(包括 CD133(Prominin-1))实现了 CSC 的富集,但当前 CSC 标志物在肿瘤维持中的作用仍不清楚。我们在患者标本中研究了神经胶质瘤干细胞(GSC)的血管周围微环境,以确定具有功能意义的富集标志物,并鉴定整合素 alpha6 为候选标志物。整合素 alpha6 与传统的 GSC 标志物共表达,并富集 GSCs。在 GSCs 中靶向整合素 alpha6 可抑制自我更新、增殖和肿瘤形成能力。我们的研究结果表明,GSCs 表达高水平的整合素 alpha6,它不仅可以作为富集标志物,也可以作为一种有前途的抗神经胶质瘤治疗方法。