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首页> 外文期刊>Oncogene >Highly purified CD44|[plus]| prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells
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Highly purified CD44|[plus]| prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells

机译：高度纯化的CD44 | [plus] |来自异种移植人类肿瘤的前列腺癌细胞富含致瘤和转移祖细胞

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CD44 is a multifunctional protein involved in cell adhesion and signaling. The role of CD44 in prostate cancer (PCa) development and progression is controversial with studies showing both tumor-promoting and tumor-inhibiting effects. Most of these studies have used bulk-cultured PCa cells or PCa tissues to carry out correlative or overexpression experiments. The key experiment using prospectively purified cells has not been carried out. Here we use FACS to obtain homogeneous CD44+ and CD44- tumor cell populations from multiple PCa cell cultures as well as four xenograft tumors to compare their in vitro and in vivo tumor-associated properties. Our results reveal that the CD44+ PCa cells are more proliferative, clonogenic, tumorigenic, and metastatic than the isogenic CD44- PCa cells. Subsequent molecular studies demonstrate that the CD44+ PCa cells possess certain intrinsic properties of progenitor cells. First, BrdU pulse-chase experiments reveal that CD44+ cells colocalize with a population of intermediate label-retaining cells. Second, CD44+ PCa cells express higher mRNA levels of several 'stemness' genes including Oct-3/4, Bmi, -catenin, and SMO. Third, CD44+ PCa cells can generate CD44- cells in vitro and in vivo. Fourth, CD44+ PCa cells, which are AR-, can differentiate into AR+ tumor cells. Finally, a very small percentage of CD44+ PCa cells appear to undergo asymmetric cell division in clonal analyses. Altogether, our results suggest that the CD44+ PCa cell population is enriched in tumorigenic and metastatic progenitor cells.
机译：CD44是一种参与细胞黏附和信号传导的多功能蛋白质。 CD44在前列腺癌（PCa）发育和进展中的作用引起争议，研究显示肿瘤促进作用和肿瘤抑制作用均如此。这些研究大多数使用大量培养的PCa细胞或PCa组织进行相关或过表达实验。尚未进行使用前瞻性纯化细胞的关键实验。在这里，我们使用FACS从多个PCa细胞培养物中以及四个异种移植肿瘤中获得均质的CD44 +和CD44-肿瘤细胞群，以比较它们的体外和体内肿瘤相关特性。我们的结果表明，CD44 + PCa细胞比同基因的CD44- PCa细胞更具增殖性，克隆性，致瘤性和转移性。随后的分子研究表明，CD44 + PCa细胞具有祖细胞的某些固有特性。首先，BrdU脉冲追踪实验揭示CD44 +细胞与一群中间标记保留细胞共定位。其次，CD44 + PCa细胞表达包括“ Oct-3 / 4”，“ Bmi”，“-catenin”和“ SMO”在内的多个“干性”基因的较高mRNA水平。第三，CD44 + PCa细胞可以在体外和体内产生CD44-细胞。第四，AR44的CD44 + PCa细胞可以分化为AR +肿瘤细胞。最后，在克隆分析中，很小比例的CD44 + PCa细胞似乎经历了不对称细胞分裂。总而言之，我们的结果表明CD44 + PCa细胞群体富含致瘤和转移祖细胞。

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