TOPIC: Use and misuse of thyroid cancer cell lines
Title: DNA profiling analysis of 40 human thyroid cancer cell lines reveals cross-contamination resulting in cell line redundancy and mis-identification.
Authors: Schweppe RE, Kloppe JP, Korch C, Pugazhenthi U, Benezra M, Knauf JA, Fagin JA, Marlow L, Copland JA, Smallridge RC, & Haugen BR.
Reference: Journal of Clinical Endocrinology & Metabolism 2008 ( ahead of print August 19 as doi:10.1210/jc.2008-1102)
Background & Objective
Cell lines derived from human cancers provide critical tools to study disease mechanisms and develop novel therapies. Recent reports indicate that up to 36% of cell lines are cross-contaminated. The authors evaluated 40 reported thyroid cancer-derived cell lines using short tandem repeat (STR) and single nucleotide polymorphism (SNP) array analysis.
Only 23 of 40 cell lines tested had unique genetic profiles. Many other cell lines were found to be derivatives of the same cell line. The misidentified cell lines included the DRO90-1 which matched the melanoma-derived cell line, A-375; the ARO81-1 and its derivatives matched the HT-29 colon cancer cell line; and the NPA87 and its derivatives matched the M14/MDA-MB-435S melanoma cell line.
These results demonstrate that many human cell lines widely used in thyroid cancer research for the past twenty years are not of thyroid origin. These results emphasize the importance of cell line integrity and characterization.
In the past 20-30 years, many laboratories have attempt to discover the mechanism of thyroid cancer development and progression, and to define novel therapies based on the results of in vitro studies performed on several thyroid cancer cell lines. In addition, many clinical researchers have conducted clinical trials in vivo based on the information gained by such basic science. Now the study by Schweppe et al. discloses that out of 40 supposed thyroid cancer cell lines, 20 of them (50%) are not only redundant (i.e., derived from the same cell line) but also misidentified (i.e., not of thyroidal origin). The misidentified cell lines matched several melanoma-derived cell lines or colon cancer cell lines. The remaining cell lines proved to be of unique origin from the thyroid, were found to express thyroid specific genes (Pax 8 and TTF1) in some cases or did not express these markers and were believed to represent anaplastic thyroid cancer that lost expression of thyroid specific genes. Cell line cross-contamination and mis-identification is a longstanding problem and redundancy among thyroid cancer cell lines has been reported also in other studies. For instance, it has been reported that one papillary thyroid cancer derived cell line (the ONCO-DG-1) is actually a derivative of an ovarian cancer cell line (the OVCAR-3). This finding has also been confirmed in the present study.
Altogether, present findings by Schweppe et al. are somehow shocking and open the field to a series of questions on the meaning of excellent studies published using misidentified thyroid cancer cell lines. We should probably revisit critically these studies and for the future thyroid cancer should be studied on cell lines that have been well defined regarding their origin according to DNA profiling analysis.
Summary and commentary prepared by Furio Pacini (Related to Chapter 18 of TDM)