New Research Sheds Light on Tumor Spread

Thursday February 1 11:14 AM ET

By Emma Patten-Hitt

NEW YORK (Reuters Health) - Three teams of researchers have discovered how tumors create vessels that carry lymph--the colorless fluid that drains into the lymph nodes and clears the body of infections. Because the lymph system is one way in which tumors spread, blocking this "highway building'' process may help halt the spread of cancer--a process known as metastasis that is the number one killer of cancer patients.

Three reports in February's issue of Nature Medicine describe researchers' attempts to understand more about that process.

It appears that new vessel growth is triggered by a specific protein, called vascular endothelial growth factor (VEGF), which interacts with a receptor on the surface of cells called the VEGF receptor. The three teams discovered that two VEGF subtypes--VEGF-C and VEGF-D--are the key players in the formation of new lymph vessels.

In one study performed in mice, Dr. Steven Stacker of the Ludwig Institute for Cancer Research, Melbourne, Australia and colleagues, found that a certain molecule stimulated VEGF-D, leading to the growth of vessels inside tumors and the spread of cells to lymph nodes. Blocking VEGF-D with an antibody, however, halted the spread of the cells.

In another study, Dr. Michael Detmar of Massachusetts General Hospital, Boston and colleagues, transplanted human breast tumors into mice. They found that cells engineered to produce extra-high levels of VEGF-C were much more likely to spread to the lymph nodes and lungs.

"This could provide a new target for therapy,'' said Detmar in a prepared statement. "By blocking the interaction of VEGF-C with its receptor on the lymphatic system, we may be able to block metastasis from occurring.''

In the third study, Dr. Kari Alitalo and colleagues, of the University of Helsinki, Finland, showed that a form of the VEGF receptor can block VEGF-C and VEGF-D in genetically engineered mice. The receptor blocked the formation of new lymph vessels and caused vessels that had already formed to regress.

Alitalo speculates that this might form the basis of a treatment for human lymphedema, a swelling of the limbs due to faulty lymph drainage.

"On the basis of our results, I would be very optimistic about the possibility of future treatment of lymphedema,'' Alitalo told Reuters Health.

In a related editorial, Dr. Karl H. Plate from the Erlangen-N Jurnberg University, Germany, notes that these studies provide the first direct experimental evidence that tumors can trigger the growth of new lymph vessels. Until now, it wasn't entirely clear how important this process is to the spread of cancer.

However, Plate noted that all the studies were conducted in animals and these results need to be tested for human cancers as well.

"If the results are true, then inhibition of this pathway could be a tool to treat and prevent cancer from spreading through the lymph system,'' he told Reuters Health.

SOURCE: Nature Medicine 2001;7:151-152, 186-191, 192-198, 199-205.

*** POSTED DECEMBER 8, 2000 ***