Uro-Oncology Research, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX.
Int J Cancer. 2019 Oct 15;145(8):2249-2259. doi: 10.1002/ijc.32370. Epub 2019 May 10.
Though human prostate cancer (PCa) heterogeneity can best be studied using multiple cell types isolated from clinical specimens, the difficulty of establishing cell lines from clinical tumors has hampered this approach. In this proof-of-concept study, we established a human PCa cell line from a prostatectomy surgical specimen without the need for retroviral transduction. In a previous report, we characterized the stromal cells derived from PCa specimens. Here, we characterized the epithelial cells isolated from the same tumors. Compared to the ease of establishing prostate stromal cell lines, prostatic epithelial cell lines are challenging. From three matched pairs of normal and tumor tissues, we established one new PCa cell line, HPE-15. We confirmed the origin of HPE-15 cells by short tandem repeat microsatellite polymorphism analysis. HPE-15 cells are androgen-insensitive and express marginal androgen receptor, prostate-specific antigen and prostate-specific membrane antigen proteins. HPE-15 expresses luminal epithelial markers of E-cadherin and cytokeratin 18, basal cell markers of cytokeratin 5 and p63 and neuroendocrine marker of chromogranin A. Interestingly, HPE-15 Cells exhibited no tumorigenicity in different strains of immune-deficient mice but can become tumorigenic through interaction with aggressive cancer cell types. HPE-15 cells can thus serve as an experimental model for the study of PCa progression, metastasis and tumor cell dormancy.
虽然使用从临床标本中分离的多种细胞类型可以最好地研究人类前列腺癌(PCa)异质性,但从临床肿瘤中建立细胞系的困难阻碍了这种方法。在这项概念验证研究中,我们无需逆转录病毒转导即可从前列腺切除术标本中建立人 PCa 细胞系。在之前的报告中,我们对源自 PCa 标本的基质细胞进行了特征描述。在这里,我们对从同一肿瘤中分离出的上皮细胞进行了特征描述。与建立前列腺基质细胞系的容易程度相比,前列腺上皮细胞系具有挑战性。从三对配对的正常和肿瘤组织中,我们建立了一种新的 PCa 细胞系 HPE-15。我们通过短串联重复微卫星多态性分析确认了 HPE-15 细胞的起源。HPE-15 细胞对雄激素不敏感,并表达边缘雄激素受体、前列腺特异性抗原和前列腺特异性膜抗原蛋白。HPE-15 表达腔上皮标志物 E-钙粘蛋白和角蛋白 18、基底细胞标志物角蛋白 5 和 p63 以及神经内分泌标志物嗜铬粒蛋白 A。有趣的是,HPE-15 细胞在不同免疫缺陷小鼠品系中无致瘤性,但通过与侵袭性癌细胞类型的相互作用可致瘤。因此,HPE-15 细胞可作为研究 PCa 进展、转移和肿瘤细胞休眠的实验模型。