Kusumbe Anjali P, Mali Avinash M, Bapat Sharmila A
National Centre for Cell Science, NCCS Complex, Pune, India.
Stem Cells. 2009 Mar;27(3):498-508. doi: 10.1634/stemcells.2008-0868.
Recruitment and localization of endothelial precursors within tumors is a potential area for the development of therapeutics, because their functional contribution to tumor vasculature is realized to be important for cancer cell survival. However, the exact nature of the recruited cell type and cellular events orchestrating the entire phenomenon remains obscure. We report that human ovarian cancer is frequently associated with cells expressing the stem cell surface marker CD133. We further show that these CD133-expressing cells are nontumorigenic in nature, and they augment tumor development through their vasculogenic potential. This cell population is attracted by cancer stem cells (CSCs) and retains a direct physical association within the CSC-derived spheroids. Our study further delineates the contribution of these vasculogenic CD133(+) stem cells, termed by us as endothelial stem cells (EnSCs) to the developing tumor vasculature during disease progression. In support of their being stem cells, the EnSCs have a capability of establishing an entire endothelial cell hierarchy. We conclude that such EnSCs play a crucial role in ensuring the development of long-term tumor vasculature to complement CSC-driven tumor development and disease progression.
肿瘤内内皮前体细胞的募集和定位是治疗学发展的一个潜在领域，因为它们对肿瘤血管系统的功能贡献被认为对癌细胞存活很重要。然而，所募集细胞类型的确切性质以及协调整个现象的细胞事件仍不清楚。我们报告，人类卵巢癌常与表达干细胞表面标志物CD133的细胞相关。我们进一步表明，这些表达CD133的细胞本质上是非致瘤性的，并且它们通过其血管生成潜能促进肿瘤发展。这群细胞被癌症干细胞（CSCs）吸引，并在CSC衍生的球体中保持直接的物理关联。我们的研究进一步描述了这些血管生成性CD133(+)干细胞，我们将其称为内皮干细胞（EnSCs）在疾病进展过程中对发育中的肿瘤血管系统的贡献。为支持其作为干细胞的特性，EnSCs具有建立完整内皮细胞层级的能力。我们得出结论，此类EnSCs在确保长期肿瘤血管系统的发育以补充CSC驱动的肿瘤发展和疾病进展方面发挥着关键作用。
