UCL Cancer Institute, CRUK Lung Cancer Centre of Excellence, University College London, London, United Kingdom.
Translational Cancer Therapeutics Laboratory, The Francis Crick Institute, London, United Kingdom.
Int J Cancer. 2018 Jul 1;143(1):160-166. doi: 10.1002/ijc.31383. Epub 2018 Apr 6.
Pre-clinical non-small cell lung cancer (NSCLC) models are poorly representative of the considerable inter- and intra-tumor heterogeneity of the disease in patients. Primary cell-based in vitro models of NSCLC are therefore desirable for novel therapy development and personalized cancer medicine. Methods have been described to generate rapidly proliferating epithelial cell cultures from multiple human epithelia using 3T3-J2 feeder cell culture in the presence of Y-27632, a RHO-associated protein kinase (ROCK) inhibitor, in what are known as "conditional reprograming conditions" (CRC) or 3T3 + Y. In some cancer studies, variations of this methodology have allowed primary tumor cell expansion across a number of cancer types but other studies have demonstrated the preferential expansion of normal epithelial cells from tumors in such conditions. Here, we report our experience regarding the derivation of primary NSCLC cell cultures from 12 lung adenocarcinoma patients enrolled in the Tracking Cancer Evolution through Therapy (TRACERx) clinical study and discuss these in the context of improving the success rate for in vitro cultivation of cells from NSCLC tumors.
临床前非小细胞肺癌(NSCLC)模型不能很好地代表患者疾病中相当大的肿瘤内和肿瘤间异质性。因此,原发性细胞体外 NSCLC 模型对于新疗法的开发和个性化癌症医学是理想的。已经描述了使用 3T3-J2 饲养细胞培养物在 RHO 相关蛋白激酶(ROCK)抑制剂 Y-27632 的存在下,从多种人上皮组织中生成快速增殖的上皮细胞培养物的方法,这些方法称为“条件重编程条件”(CRC)或 3T3+Y。在一些癌症研究中,该方法的变体允许多种癌症类型的原发性肿瘤细胞扩增,但其他研究表明,在这种情况下,正常上皮细胞从肿瘤中的优先扩增。在这里,我们报告了从参加跟踪癌症通过治疗进化(TRACERx)临床研究的 12 名肺腺癌患者中获得原发性 NSCLC 细胞培养物的经验,并在提高 NSCLC 肿瘤细胞体外培养成功率的背景下讨论了这些经验。