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Oncotarget. 2017 Feb 14;8(7):11114-11126. doi: 10.18632/oncotarget.14366.

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

Author information

1
Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
2
The Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
3
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
4
Division of Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
5
Department of Pathology, Yale University, New Haven, CT, USA.
6
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.
7
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
8
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
9
Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
10
Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
11
Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
12
Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
13
Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
14
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
15
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

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.

KEYWORDS:

cell culture; conditionally reprogrammed cells; non-small cell lung cancer; respiratory epithelial cells; rock inhibitor

PMID:
28052041
PMCID:
PMC5355251
DOI:
10.18632/oncotarget.14366
[Indexed for MEDLINE]
Free PMC Article

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