Nearly 50 years ago, researchers in Uppsala, Sweden used cells from a patient to establish a brain tumor cell line that has become widely used. But a new study suggests that the most common source of that cell line used by scientists today may not be derived from that original patient’s tumor, raising questions about the results obtained in hundreds of studies.
In a new paper out today in Science Translational Medicine, Bengt Westermark, of Uppsala University, and colleagues describe what they found when they performed a forensic DNA analysis comparing the widely used version of the cell line to the original. The findings are consistent with those of other analyses in which cell lines turn out not to be what researchers thought, a problem we’ve focused some attention on.
Here’s an email interview with Westermark about the findings and their implications:
Retraction Watch: Where does the original U87MG cell line derive from?
Bengt Westermark: The original cell line was established from a glioblastoma multiforme (the most common and most malignant form of human brain tumor) of a 44-year old woman. The cell line was established and published 1968 by my mentor in science, Jan Pontén, as part of a research program where he tried to establish human cell lines from malignant tumors. I became a student in his laboratory and picked up his idea that studies of human malignant cells in culture could lead to a better understanding of the fundamental processes that lead to a malignant transformation, i.e. how a normal cell becomes a cancer cell.
RW: What made you suspect the U87MG available from the American Type Culture Collection (ATCC) was not the cell line you thought it was?
BW: The original U87MG was difficult to culture and consisted of large flat cells. I was therefore surprised to see that so many investigators used the cell line and became suspicious. Could there be a misidentification?
RW: You found 1700 entries in PubMed using UG glioma cells. Do you have an estimate of how many research groups and/or published papers have based their findings on the ATCC version of U87MG? In other words, how many papers might contain problematic data as a result of this cell-line mixup?
BW: I would guess that the majority of these papers are based on the ATCC line.
RW: Do other tissue repositories carry U87MG? If so, could those also be contaminated?
BW: Yes, Cell Line Services for sure. They have the same STR profile as the ATCC cell line. I have not checked other repositories.
RW: Your analysis suggests the ATCC version of U87MG may also derive from a human glioma tumor – does that give you hope that some of the findings using the ATCC version might still be correct, even though they’re not using the original U87MG line?
BW: Yes. This is in the title of the paper (bad news and good news).
RW: Where do you think the ATCC version of the U87MG cell line might have originated from? Could it be HeLa cells?
BW: My personal belief, based on the expression profile of the cells, is that the cells originate from a bona fide human glioblastoma, but we lack definite proof. They are not HeLa cells.
RW: We’ve discussed many times on our site the widespread problem of misidentification of cell lines, and how to solve it – such as using a DNA profiling technique to identify cells before using them. What do you think is the best way to solve the problem of researchers using the wrong cell lines?
BW: I think that all journals should require a check of cell identity, as several already do. What we say in the paper, however, is that this may not suffice when the “original” cell line is misidentified, as U87MG. In our laboratory, as in other laboratories as well, we have established a glioblastoma cell bank from annotated tumor material. We can check the identity using patient blood as reference, so that we will high certainty can prove the origin.
(Disclosure: We have a partnership with the news side of Science, which is walled off from those who work on peer-reviewed manuscripts there.)
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