Bobek Vladimir, Hoffman Robert M, Kolostova Katarina
Department of Tumor Biology, Third Faculty of Medicine, Charles University, Prague 10010, Czech Republic.
Diagn Cytopathol. 2013 May;41(5):413-7. doi: 10.1002/dc.22843. Epub 2012 Apr 17.
Circulating tumor cells (CTC) may reach multiple organ sites. However, CTC seeding and growth in distant organs is not random. Each metastatic site may contain a specific subpopulation of the original metastatic tumor capable of growing at that site. The fluorescent orthotopic prostate cancer model (PC-3-GFP) model was used for immunomagnetic capture of CTC. The captured CTC were efficiently cultivated in vitro. PC-3-GFP cells were also isolated from various metastatic sites, grown in vitro and examined under fluorescence microscopy. The differential morphology was compared of primary tumor cells, CTC and disseminated (DTC) from multiple metastatic sites, from nude mice with orthotopic PC-3-GFP. The cultured captured CTC and DTC from various organs have distinctive morphologies. Distinct cancer cell morphologies were observed at different metastatic sites as well as among CTC. The distinct morphologies were maintained during in vitro culture. The results demonstrate extensive tumor heterogeneity that could account for the widely different behavior of cancer cells in a single tumor. Further hetereogeneity testing would be a big promise for personalizing the cancer treatment in the future.
循环肿瘤细胞(CTC)可能会到达多个器官部位。然而,CTC在远处器官的播种和生长并非随机发生。每个转移部位可能包含能够在该部位生长的原始转移性肿瘤的特定亚群。荧光原位前列腺癌模型(PC-3-GFP)被用于免疫磁捕获CTC。捕获的CTC在体外得到了有效培养。PC-3-GFP细胞也从各个转移部位分离出来,在体外培养并在荧光显微镜下进行检查。比较了原位PC-3-GFP裸鼠的原发肿瘤细胞、CTC以及来自多个转移部位的播散肿瘤细胞(DTC)的差异形态。从各个器官培养捕获的CTC和DTC具有独特的形态。在不同的转移部位以及CTC之间观察到了不同的癌细胞形态。这些独特的形态在体外培养过程中得以保持。结果表明存在广泛的肿瘤异质性,这可能解释了单个肿瘤中癌细胞行为的巨大差异。进一步的异质性检测有望在未来实现癌症治疗的个性化。