By Drs. David Niesel and Norbert Herzog
It is well established that tumors can induce our own cells to form new blood in a process called angiogenesis. This supplies tumors with the nutrients and oxygen to support their growth. But in 1999, scientists hypothesized that tumor cells themselves can form blood vessels, a process called vasculogenic mimicry or VM. That started a fierce, but healthy debate about how tumors acquire their blood supply. Nearly 17 years later, a drug that targets VM has gone into clinical trials and if successful would go a long way in bolstering the case that this phenomenon contributes to tumor growth.
It was in the early 1970's that Judah Folkman of Harvard Medical School hypothesized that tumors grow so large because they can trigger angiogenesis. He proposed to a skeptical scientific community that drugs targeting this process would starve tumors and be another approach to treating solid tumors. Several anti-angiogenesis drugs have come to market but the original optimism has been tempered by the fact that the drugs only slow tumor growth and often become resistant to these drugs. Could the alternative means of developing blood vessels, VM, account for the less than spectacular effects of anti-angiogenic drugs?
In experiments, melanoma cells from rapidly spreading tumors were grown on a gel that mimics the extracellular matrix that is embedded in the body. The aggressive melanoma cells migrated through the matrices and "scrunched it up" forming a network of channels that looked like chicken wire. Similar channel networks were also seen in melanomas growing in patient eyes. Additional work on melanomas in the eyes revealed that these channels contained red blood cells but lacked any normal blood vessel cells reinforcing the theory that the tumor cells themselves formed them. Since then, channels have been shown in tumors of the prostate, breast, kidney, lung, gall bladder, liver, ovary and bone. An analysis of 36 studies revealed that the presence of channels in tumors doubled the chances of that patient dying. Still, skeptics wonder how important and how prevalent these tumor channels are and whether they account for the ineffectiveness of anti-angiogenesis drugs.
A big question is how the tumor channels hook into the normal blood vessels. Interestingly, tumor cells that create the channels turn on the same genes and release some of the same substances that prevent blood from clotting and obstructing them. Not only do these channels help provide tumors with the nutrients and oxygen they need to grow but they could also promote a tumor's ability to spread to other parts of the body.
Interestingly, scientists have shown that blocking normal blood cell formation appears to stimulate tumor cells to form channels. A drug called CVM-1118 blocks VM by interfering with the activity of a gene called Nodal that drives this process. This drug is currently in clinical trials for treating a variety of cancers. There are several more drugs targeting VM which may provide another tool in fighting cancer. Perhaps a combination of anti-angiogenic and anti-VM cells would deprive tumors of their blood supply that helps drive their growth, spread.
Medical Discovery News is hosted by professors Norbert Herzog at Quinnipiac University, and David Niesel of the University of Texas Medical Branch. Learn more at www.medicaldiscoverynews.com.