Non-malignant respiratory epithelial cells preferentially proliferate from resected non-small cell lung cancer specimens cultured under conditionally reprogrammed conditions.

TitleNon-malignant respiratory epithelial cells preferentially proliferate from resected non-small cell lung cancer specimens cultured under conditionally reprogrammed conditions.
Publication TypeJournal Article
Year of Publication2017
AuthorsGao, B, Huang, C, Kernstine, K, Pelekanou, V, Kluger, Y, Jiang, T, Peters-Hall, JR, Coquelin, M, Girard, L, Zhang, W, Huffman, K, Oliver, D, Kinose, F, Haura, E, Teer, JK, Rix, U, Le, AT, Aisner, DL, Varella-Garcia, M, Doebele, RC, Covington, KR, Hampton, OA, Doddapaneni, H, Jayaseelan, JC, Hu, J, Wheeler, DA, Shay, JW, Rimm, DL, Gazdar, A, Minna, JD
JournalOncotarget
Volume8
Issue7
Pagination11114-11126
Date Published2017 Feb 14
ISSN1949-2553
Abstract

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.

DOI10.18632/oncotarget.14366
Alternate JournalOncotarget
PubMed ID28052041
PubMed Central IDPMC5355251
Grant ListP50 CA058187 / CA / NCI NIH HHS / United States
R01 CA181746 / CA / NCI NIH HHS / United States
P30 CA046934 / CA / NCI NIH HHS / United States
P30 CA076292 / CA / NCI NIH HHS / United States
P30 CA142543 / CA / NCI NIH HHS / United States
P50 CA070907 / CA / NCI NIH HHS / United States
U01 CA176284 / CA / NCI NIH HHS / United States
P30 CA016359 / CA / NCI NIH HHS / United States
C06 RR030414 / RR / NCRR NIH HHS / United States
T32 CA124334 / CA / NCI NIH HHS / United States
P50 CA196530 / CA / NCI NIH HHS / United States