Oncotarget

Research Papers:

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

Boning Gao, Chunxian Huang, Kemp Kernstine, Vasiliki Pelekanou, Yuval Kluger, Tingting Jiang, Jennifer R. Peters-Hall, Melissa Coquelin, Luc Girard, Wei Zhang, Kenneth Huffman, Dwight Oliver, Fumi Kinose, Eric Haura, Jamie K. Teer, Uwe Rix, Anh T. Le, Dara L. Aisner, Marileila Varella- Garcia, Robert C. Doebele, Kyle R. Covington, Oliver A. Hampton, Harsha V. Doddapaneni, Joy C. Jayaseelan, Jianhong Hu, David A. Wheeler, Jerry W. Shay, David L. Rimm, Adi Gazdar and John D. Minna _

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Oncotarget. 2017; 8:11114-11126. https://doi.org/10.18632/oncotarget.14366

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Abstract

Boning Gao1,2,3, Chunxian Huang1,2, Kemp Kernstine4, Vasiliki Pelekanou5, Yuval Kluger5, Tingting Jiang6, Jennifer R. Peters-Hall7, Melissa Coquelin7, Luc Girard1,2,3, Wei Zhang1,2, Kenneth Huffman1,2, Dwight Oliver8, Fumi Kinose9, Eric Haura9, Jamie K. Teer10, Uwe Rix11, Anh T. Le12, Dara L. Aisner13, Marileila Varella-Garcia12,13, Robert C. Doebele12, Kyle R. Covington14, Oliver A. Hampton14, Harsha V. Doddapaneni14, Joy C. Jayaseelan14, Jianhong Hu14, David A. Wheeler14, Jerry W. Shay7, David L. Rimm5, Adi Gazdar1,2,8, John D. Minna1,2,3,15

1Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA

2The Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA

3Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

4Division of Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA

5Department of Pathology, Yale University, New Haven, CT, USA

6Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA

7Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

8Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

9Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

10Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

11Department of Drug Discovery, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA

12Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

13Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

14Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA

15Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA

Correspondence to:

Adi Gazdar, email: [email protected]

John D. Minna, email: [email protected]

Keywords: conditionally reprogrammed cells, respiratory epithelial cells, non-small cell lung cancer, rock inhibitor, cell culture

Received: September 23, 2016     Accepted: December 20, 2016     Published: December 29, 2016

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.


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