Lung cancer cell lines as tools for biomedical discovery and research

Abstract

Lung cancer cell lines have made a substantial contribution to lung cancer translational research and biomedical discovery. A systematic approach to initiating and characterizing cell lines from small cell and non-small cell lung carcinomas has led to the current collection of more than 200 lung cancer cell lines, a number that exceeds those for other common epithelial cancers combined. The ready availability and widespread dissemination of the lines to investigators worldwide have resulted in more than 9000 citations, including multiple examples of important biomedical discoveries. The high (but not perfect) genomic similarities between lung cancer cell lines and the lung tumor type from which they were derived provide evidence of the relevance of their use. However, major problems including misidentification or cell line contamination remain. Ongoing studies and new approaches are expected to reveal the full potential of the lung cancer cell line panel.

Figure 1

Distribution of human tumor cell lines in the Sanger database (www.sanger.ac.uk). Of the 784 cell lines for which data were available, 154 were of lung origin. The common epithelial category group includes breast, colorectal, prostate, gastric, and hepatic cancers. The “other” group includes all other types of human cancers listed in the database. CNS = central nervous system.

Figure 2

Regions of frequent amplification and deletion in lung adenocarcinoma cell lines and tumors. A) Alteration frequency. Thirty-three lung adenocarcinoma cell lines and 169 tumor samples were analyzed by use of a whole-genome tiling path array for comparative genomic hybridization analysis (33). Genomic imbalances were identified by use of aCGH-Smooth (34), and the frequency of alteration across all samples in each group was determined as described previously (35). The resulting alteration frequencies are displayed across the entire human genome with amplifications on the left and deletions on the right. For each chromosome, the shaded portion represents the p arm. Chromosome location is depicted on the left of the histograms with the p and q arms separated by differential shading (gray and white, respectively). The genomic similarity between the cell lines and tumors is evident by the close association of the plots. B) Commonly reported sites of amplification and deletion that are frequently altered (>15% of samples) in both cell line and tumor samples. Frequency values for chromosome bands were generated as described above. Known oncogenes and tumor suppressor genes that are located in each region are shown.

Figure 3

Verification of the identity of lung cancer cell lines. Representative electropherograms from PowerPlex fingerprint analyses are shown that verify the identity of cell lines from different sources. For sample analysis, the allele sizes of the nine polymorphic markers analyzed are displayed below the electropherograms. The electropherogram results of one marker (boxed and also identified to the left) are displayed. When at least seven of the nine markers matched, the cell lines are assumed to be identical. A) Match of cell lines H1993 and H2073. Both cell lines were isolated from the same patient and, thus, this represents a match. B) Match of B lymphoblastoid cell line BL1184 and non–small cell lung cancer cell line H1184. Both cell lines were isolated from the same patient. C) Incorrect attribution. BL1171 cells (middle) match BL2195 cells as a result of cell line cross-contamination or mislabeling. Note that full designations of the cell lines include the prefix NCI (eg, NCI-BL1171).

Figure 4

Number of citations for human lung cancer cell lines. Data were obtained from a search of the PubMed database from within the EndNote program by use of the medical search heading terms “lung neoplasms”; “cell line, tumor”; and “humans.” The cumulative number of citations and the number of citations per 5 years are shown. The results are from a search performed in June 2010. NCI = National Cancer Institute; NSCLC = non–small cell lung cancer; SCLC = small cell lung cancer.