Authenticating Cell Lines in Ophthalmic Research Laboratories

ture, Lacroix1 examined the issue of cross-contamination of cell lines including the well-known contamination of cell lines with HeLa cells,2 and the misidentification of the ECV304 cell line as "immortalized endothelial cells" when these cells in fact originated from T24 bladder carcinoma cells.3 Lacroix1 esti- mated that between 18% and 36% of cell lines have been misclassified. One survey at a large research institution sug- gested that fewer than 50% of researchers authenticate their cell lines.4 Nardone5 proposed recently that identification of cell lines be required of investigators before grants are awarded, and the National Institutes of Health subsequently called for researchers to authenticate cell lines as a prerequisite for grant funding.6 Cell lines are widely used in ophthalmic investigations. The authors' own research efforts have been focused on the biol- ogy of metastasis of uveal melanoma, and in the field of ocular oncology research, the use of cell lines is critical for at least two reasons. First, there are no animal models of spontaneous uveal melanoma that faithfully replicate the behavior of the human disease.7 Transgenic models of uveal melanoma do not reproduce histogenesis of human uveal melanoma, and spon- taneous uveal melanomas develop too sporadically in nature to be valuable in research,8-13 or the animal melanoma tumors vary significantly from their human counterparts.14 Therefore, uveal melanoma researchers have increasingly relied on the implantation of animal and human melanoma cell lines into animals to model the behavior of human uveal melanoma to improve imaging techniques15-17 and to investigate immuno- logic18,19 and molecular mechanisms of tumor behavior.20,21 Second, mindful of the reality that statistical associations between histologic characteristics and outcome do not always indicate causality, the availability of cell lines allows ophthal- mic researchers to advance from correlative studies to mech- anistic investigations using advanced molecular methodolo- gies. For example, All-Ericsson et al.22 identified the association between the expression of insulin-like growth factor-1 by im-