Verification and unmasking of widely used human esophageal adenocarcinoma cell lines

Abstract

For decades, hundreds of different human tumor type-specific cell lines have been used in experimental cancer research as models for their respective tumors. The veracity of experimental results for a specific tumor type relies on the correct derivation of the cell line. In a worldwide effort, we verified the authenticity of all available esophageal adenocarcinoma (EAC) cell lines. We proved that the frequently used cell lines SEG-1 and BIC-1 and the SK-GT-5 cell line are in fact cell lines from other tumor types. Experimental results based on these contaminated cell lines have led to ongoing clinical trials recruiting EAC patients, to more than 100 scientific publications, and to at least three National Institutes of Health cancer research grants and 11 US patents, which emphasizes the importance of our findings. Widespread use of contaminated cell lines threatens the development of treatment strategies for EAC.

Figure 1

Authentication of human esophageal adenocarcinoma cell line OE33. A and B) Hematoxylin- and eosin-stained sections of the original tissue and xenograft of OE33 showing a poorly differentiated adenocarcinoma. C) In vitro growth pattern of cell line OE33. D) Short tandem repeat profile of the primary normal tissue (P) and cell line OE33 (C) indicating correct derivation of the cell line. Short-term repeat loci are indicated in boxes above electropherogram; the number of repeat units is indicated below the peaks. Note: loss of heterozygosity in the cell line at loci TH01 and FGA. The additional allele (11 repeat units) of D8S1179 observed in cell line OE33 is a known phenomenon and is probably due to somatic mutation or localized chromosomal rearrangements at this heterozygous locus.