期刊
ONCOTARGET
卷 8, 期 7, 页码 11114-11126出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.14366
关键词
conditionally reprogrammed cells; respiratory epithelial cells; non-small cell lung cancer; rock inhibitor; cell culture
资金
- National Cancer Institute Specialized Program of Research Excellence in Lung Cancer SPORE [P50CA70907, P50CA058187]
- NCI Designated Comprehensive Cancer Center [P30CA142543, P30CA016359, P30CA076292, P30CA046934, T32 CA124334]
- Cystic Fibrosis Foundation Postdoctoral Fellowship
- Cystic Fibrosis Foundation [SHAY15XX0]
- Gilead Sciences
- Cancer Prevention and Research Institute of Texas (CPRIT) [RP110708]
- National Cancer Institute [UO1 CA176284]
- National Institutes of Health [C06 RR30414]
The conditionally reprogrammed cells (CRC) method, using a Rho kinase inhibitor and irradiated mouse fibroblast cells has been described for the efficient growth of cells from malignant and non-malignant samples from primary tumor and non-malignant sites. Using the CRC method, four institutions independently cultured tumor tissues from 48 non-small cell lung cancers (NSCLC, mostly from primary resected tumors) and 22 non-malignant lungs. We found that epithelial cells could be cultured from tumor and non-malignant lung. However, epithelial cells cultured from tumors had features of non-malignant respiratory epithelial cells which include: 1) among 22 mutations found in the original tumors only two mutations were found in the CRC cultures with reduced frequency (31% to 13% and 92% to 15% from original tumor and CRC culture respectively); 2) copy number variation was analyzed in 9 tumor and their CRC cultures and only diploid patterns were found in CRC cultures; 3) mRNA expression profiles were similar to those of normal respiratory epithelial cells; and 4) co-culture of tumor and non-malignant lung epithelial cells resulted in mostly non-malignant cells. We conclude that CRC method is a highly selective and useful method for the growth of non-malignant respiratory epithelial cells from tumor specimens and only occasionally do such CRC cultures contain a small subpopulation of cancer cells marked by oncogenic mutations. While our findings are restricted to resected primary NSCLC, they indicated the necessity to fully characterize all CRC cultures and the need to develop culture technology that facilitates the growth of primary lung cancers.
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