Expansion of airway basal epithelial cells from primary human non-small cell lung cancer tumors

Int J Cancer. 2018 Jul 1;143(1):160-166. doi: 10.1002/ijc.31383. Epub 2018 Apr 6.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01888601.

Keywords: basal cells; cell culture; epithelial cells; lung cancer; stem/progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Aged
  • Aged, 80 and over
  • Amides / pharmacology
  • Animals
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Proliferation
  • Coculture Techniques / methods*
  • Epithelial Cells / cytology*
  • Epithelial Cells / pathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Transplantation
  • Pyridines / pharmacology
  • Respiratory Mucosa / cytology
  • Sequence Analysis, DNA
  • Tumor Cells, Cultured

Substances

  • Amides
  • Pyridines
  • Y 27632

Associated data

  • ClinicalTrials.gov/NCT01888601