Department of Medicine, Northwestern University, United States.
Department of Medicine, Northwestern University, United States; Robert H. Lurie Cancer Center, Northwestern University, United States; Center for Molecular Innovation and Drug Discovery, Northwestern University, United States.
Cancer Lett. 2014 Oct 1;352(2):179-86. doi: 10.1016/j.canlet.2014.06.012. Epub 2014 Jul 10.
With prostate cancer (PCa), circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) portend a poor clinical prognosis. Their unknown biology precludes rational therapeutic design. We demonstrate that CTC and DTC cell lines, established from mice bearing human PCa orthotopic implants, exhibit increased cellular invasion in vitro, increased metastasis in mice, and express increased epithelial to mesenchymal transition biomarkers. Further, they are selectively resistant to growth inhibition by mitoxantrone-like agents. These findings demonstrate that CTC formation is accompanied by phenotypic progression without obligate reversion. Their increased metastatic potential, selective therapeutic resistance, and differential expression of potential therapeutic targets provide a rational basis to test further interventions.
对于前列腺癌（PCa）而言，循环肿瘤细胞（CTC）和播散性肿瘤细胞（DTC）预示着不良的临床预后。它们未知的生物学特性妨碍了合理的治疗设计。我们证明，从患有人类 PCa 原位植入物的小鼠中建立的 CTC 和 DTC 细胞系，在体外表现出更高的细胞侵袭性，在小鼠中具有更高的转移能力，并且表达更高的上皮到间充质转化生物标志物。此外，它们对米托蒽醌样药物的生长抑制具有选择性抗性。这些发现表明，CTC 的形成伴随着表型进展，而不一定需要逆转。它们更高的转移潜力、选择性治疗抵抗以及潜在治疗靶点的差异表达为进一步干预提供了合理的基础。
