This week, it was reported that scientists at the UNC School of Medicine found a previously unknown subpopulation of melanoma cells. These cells, which mimic non-cancerous cells, could provide scientists with another target for cancer therapy. These particular cells help tumors to resist medicines which are designed to block the formation of blood vessels.
The team pointed out that there are many therapies which try to starve tumors off, but that many of these therapies have not worked as well as hoped. They believe that these previously unknown cells may be one of the reasons why.
Most of the drugs developed to disrupt tumor blood vessels target a protein called vascular endothelial growth factor, or VEGF, which is part of a major signaling pathway in the noncancerous endothelial cells that typically line blood vessels in tumors. But other research has suggested that tumors are able to resist anti-angiogenic therapies – particularly those targeting VEGF – through a variety of complex mechanisms. In one set of experiments, Dudley and graduate student James Dunleavey, used a known anti-angiogenic drug which blocks VEGF and found that this new subpopulation of melanoma cells was more prevalent in drug-resistant tumors in mouse tumor models. Moreover, tumors composed entirely by this new subpopulation in mouse models did not respond at all to anti-VEGF therapy.
Dunleavey first separated non-cancerous cells from melanoma cells. Genetic testing found that these non-cancerous cells did not possess the biomarkers common for these cells, however. These cells didn’t express VEGF receptors, which perhaps explained why anti-VEGF therapy wasn’t working. Now the team had to figure out what these cells were.
Upon conducting more research, it was found that these cells had many similar characteristics to melanoma cells. This included a protein called PECAM1. This protein helps which adhesion, particularly in the formation of blood vessels. When the team looked into blood vessels formed with PECAM1 tumors, they found melanoma cells.
Dudley and Dunleavey then teamed up with other scientists, including UNC’s Paul Dayton, PhD, a professor in the Department of Biomedical Engineering, member of the UNC Lineberger Comprehensive Cancer Center, and co-author on the Nature Communications paper. Dayton’s lab conducted ultrasound imaging studies showing that PECAM1-positive tumor blood vessels in mice had twice the vascular density of PECAM1-negative vessels. And the blood volume of PECAM1-positive blood vessels was 4 ½ times greater than PECAM1-negative vessels. This showed the researchers that these newly discovered PECAM1-positive melanoma cells had a real effect on the function of tumor blood vessels.
The team thinks that these cells help tumor cells to interact with non-cancerous cells. These interactions could be helping the tumors to resist anti-angiogenic therapies.
We at MoleSafe applaud this team for their discoveries. They could be an important step in the fight against melanoma.
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