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Metastatic tumors trigger new vessels early

NEW YORK, Jan 18 (Reuters Health) -- Metastatic tumors -- tumors that arise secondary to an original tumor -- form new blood vessels at a very early stage in mice and rats, when the tumor consists of only 60 to 80 cells, researchers report.

The finding may lead to new therapies aimed at preventing cancers from growing or spreading.

New blood vessel formation is known as angiogenesis. "Contrary to previous reports, we found out that tumor cells can initiate angiogenesis very early, instead of when they grew to 1 or 2 millimeters, which would contain millions of cells," Dr. Chuan-Yuan Li told Reuters Health.

"So this means that chemotherapeutic agents, for example, may be able to access these tumor cells very early on," he added. "Using angiogenesis inhibitors, you may be able to block tumor growth at very early times." Li and colleagues at Duke University Medical Center in Durham, North Carolina, injected 20 to 50 rat or mouse breast cancer cells under the skin of rats or mice, respectively. The tumor cells had been modified with a gene that caused the cells to glow green, allowing the researchers to follow the growth of the tumor at high resolution.

By day 4, cells could be seen proliferating and migrating towards existing blood vessels. Further signs of angiogenesis were observed by day 6, when the tumor consisted of only 60 to 80 cells. By day 8, when the tumor consisted of 300 to 400 cells, functional blood vessels containing red blood cells were observed. The researchers estimated that blood vessels must have started to form by day 6 or 7, when approximately 100 to 300 cells were present.

In particular, tumor cells divided and migrated towards target blood vessels and seemed to align themselves along the new vessels, suggesting "active 'cross-talk' during the early stages of tumor growth," according to the authors. The report is published in the January 19th issue of the Journal of the National Cancer Institute.

Next, Li's group injected mice with a shortened form of the receptor for vascular endothelial growth factor. "It basically soaks up a very potent angiogenesis factor called vascular endothelial growth factor. It binds to the growth factor, but cannot translate its signal," Li explained.

When injected along with 40 to 50 tumor cells, the protein completely inhibited tumor growth in 4 of 6 cases, with all tumor cells disappearing within 5 days. In the other 2 cases, tumor growth was either slowed down substantially or reversed.

Although this research mainly applies to metastatic tumors, Li points out that metastasis is a major problem in cancer therapy. His group plans to try other angiogenesis inhibitors, since they think that multiple proteins are probably involved in angiogenesis.


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