Cell discovery may lead to new generation of cancer therapies

A newly discovered subpopulation of melanoma cancer cells may lead to the development of more effective cancer therapies.

Researchers at the University of North Carolina School of Medicine, Chapel Hill, have pinpointed a set of intriguing characteristics in this cell subpopulation, which they found in the blood vessels of tumors. The cells, which mimic noncancerous endothelial cells that normally populate blood vessels in tumors, could provide researchers with another target for cancer therapies.

The study, published Oct. 22 in Nature Communications, shows how these particular melanoma cells help tumors resist anti-angiogenic drugs.

“For a long time the hope has been that anti-angiogenic therapies would starve tumors of the nutrients they need to thrive, but these drugs haven’t worked as well as we all had hoped,” lead author Andrew C. Dudley, Ph.D., assistant professor in the department of cell biology and physiology, says, in a news release. “There are likely several reasons why these drugs haven’t been effective, (and) our research suggests that these previously uncharacterized cells could be one of the reasons.”

According to the study, most drugs developed to disrupt tumor blood vessels target the protein VEGF (vascular endothelial growth factor), which is part of a major signaling pathway in the noncancerous endothelial cells that line tumor blood vessels. Past research, however, has found that tumors are able to resist anti-angiogenic therapies - particularly those targeting VEGF - through a variety of complex mechanisms. The researchers used a known anti-angiogenic drug that blocks VEGF and found that the new melanoma cells were more prevalent in drug-resistant tumors in mouse tumor models. Moreover, tumors composed entirely of the new subpopulation in mouse models did not respond at all to anti-VEGF therapy.

The researchers wrote that the new cells may help allow tumor cells to interact in specific ways with true endothelial cells, and that this interaction, combined with unresponsive VEGF, could help blood vessels resist therapies designed to destroy them. They added that their research further elucidates the complex nature of human tumors, which are not comprised of the same type of cancer cell but are a mix of different cell types with different functions.

The study suggests there may be a need to develop a combination of anti-angiogenic drugs to attack the endothelial cells that form blood vessels and the tumor cells that might form blood-filled channels in tumors.

Reference: Dunleavey JM, Xiao L, Thompson J, et al. Vascular channels formed by subpopulations of PECAM1⁺ melanoma cells. Nat Commun. 22 Oct 2014 [Epub ahead of print] http://www.nature.com/ncomms/2014/141022/ncomms6200/full/ncomms6200.html

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