Laboratory of Rare Human Circulating Cells (LCCRH), Department of Cellular and Tissular Biopathology of Tumors, University Medical Centre, Montpellier, France. EA2415 - Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research, Montpellier University, Montpellier, France.
Department of Medical Oncology, University Medical Centre, Montpellier, France.
Cancer Res. 2015 Mar 1;75(5):892-901. doi: 10.1158/0008-5472.CAN-14-2613. Epub 2015 Jan 15.
Circulating tumor cells (CTC) in blood are promising new biomarkers potentially useful for prognostic prediction and monitoring of therapies in patients with solid tumors including colon cancer. Moreover, CTC research opens a new avenue for understanding the biology of metastasis in patients with cancer. However, an in-depth investigation of CTCs is hampered by the very low number of these cells, especially in the blood of patients with colorectal cancer. Thus, the establishment of cell cultures and permanent cell lines from CTCs has become the most challenging task over the past year. Here, we describe, for the first time, the establishment of cell cultures and a permanent cell line from CTCs of one patient with colon cancer. The cell line designated CTC-MCC-41 has been cultured for more than one year, and the cells have been characterized at the genome, transcriptome, proteome, and secretome levels. This thorough analysis showed that CTC-MCC-41 cells resemble characteristics of the original tumor cells in the patient with colon cancer and display a stable phenotype characterized by an intermediate epithelial/mesenchymal phenotype, stem cell-like properties, and an osteomimetic signature, indicating a bone marrow origin. Functional studies showed that CTC-MCC-41 cells induced rapidly in vitro endothelial cell tube formation and in vivo tumors after xenografting in immunodeficient mice. The establishment of this first colon cancer CTC line allows now a wealth of functional studies on the biology of CTCs as well as in vitro and in vivo drug testing.
循环肿瘤细胞(CTC)在血液中是很有前途的新型生物标志物,可能对包括结肠癌在内的实体瘤患者的预后预测和治疗监测有用。此外,CTC 的研究为理解癌症患者转移的生物学打开了新的途径。然而,由于这些细胞的数量非常少,特别是在结直肠癌患者的血液中,对 CTC 进行深入研究受到了阻碍。因此,建立 CTC 的细胞培养物和永久细胞系成为了过去一年中最具挑战性的任务。在这里,我们首次描述了从一名结肠癌患者的 CTC 中建立细胞培养物和永久细胞系的过程。该细胞系被命名为 CTC-MCC-41,已经培养了一年多,并且在基因组、转录组、蛋白质组和分泌组水平对其进行了特征描述。这项全面的分析表明,CTC-MCC-41 细胞类似于患者结肠癌原始肿瘤细胞的特征,并表现出稳定的表型,具有中间上皮/间充质表型、干细胞样特性和骨模仿特征,表明其来源于骨髓。功能研究表明,CTC-MCC-41 细胞在体外诱导内皮细胞管形成和体内异种移植免疫缺陷小鼠后形成肿瘤的速度很快。该结肠癌 CTC 系的建立,现在可以进行大量关于 CTC 生物学的功能研究,以及体外和体内药物测试。