Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Cancer Cell. 2013 Feb 11;23(2):171-85. doi: 10.1016/j.ccr.2012.12.021. Epub 2013 Jan 31.
We report a paracrine effect whereby endothelial cells (ECs) promote the cancer stem cell (CSC) phenotype of human colorectal cancer (CRC) cells. We showed that, without direct cell-cell contact, ECs secrete factors that promoted the CSC phenotype in CRC cells via Notch activation. In human CRC specimens, CD133 and Notch intracellular domain-positive CRC cells colocalized in perivascular regions. An EC-derived, soluble form of Jagged-1, via ADAM17 proteolytic activity, led to Notch activation in CRC cells in a paracrine manner; these effects were blocked by immunodepletion of Jagged-1 in EC-conditioned medium or blockade of ADAM17 activity. Collectively, ECs play an active role in promoting Notch signaling and the CSC phenotype by secreting soluble Jagged-1.
我们报告了一种旁分泌效应，即内皮细胞（ECs）促进人结直肠癌（CRC）细胞的癌症干细胞（CSC）表型。我们表明，在没有直接细胞-细胞接触的情况下，ECs 通过 Notch 激活分泌促进 CRC 细胞 CSC 表型的因子。在人 CRC 标本中，CD133 和 Notch 细胞内结构域阳性的 CRC 细胞在血管周围区域共定位。EC 衍生的、可溶性形式的 Jagged-1 通过 ADAM17 蛋白水解活性，以旁分泌的方式导致 CRC 细胞中的 Notch 激活；这些作用可以通过免疫耗尽 EC 条件培养基中的 Jagged-1 或阻断 ADAM17 活性来阻断。总之，ECs 通过分泌可溶性 Jagged-1 积极促进 Notch 信号和 CSC 表型。
