The study authors, led by Michael Detmar, MD, a dermatologist at Massachusetts General Hospital's Cutaneous Biology Research Center (CBRC) used a new technique to show "that a system of lymphatic vessels grows within cancers." Doctors have long known that the first place most types of cancer cells spread to is the lymph nodes, bean-sized collections of immune system cells. They also knew that cancer cells spread to these lymph nodes through small vein-like channels called lymphatic vessels. Until now, scientists could recognize lymphatic channels at the edges of cancerous tumors, but they could not prove that the channels also were present inside the tumors.

Using a new method, Detmar, along with Mihaela Skobe, PhD, a postdoctoral fellow, and their colleagues have shown that cancer cells produce a substance that causes lymphatic vessels to form inside the tumors, not just at their edges. They also found that cells releasing the highest levels of this substance, called VEGF-C (vascular endothelial growth factor-C), formed tumors containing the greatest number of lymphatic vessels. And, according to Detmar, "There is almost a 100% correlation between this lymphatic system and metastasis." In other words, the more lymphatic vessels there were inside the tumor, the more cancer cells had spread to the lymph nodes and lungs (outside the tumor).

Detmar and Skobe began their experiment by implanting human breast cancer cells into the breast tissue of mice. Some mice were injected with breast cancer cells that had been genetically altered to produce high levels of VEGF-C, which stimulated the growth of lymphatic vessels.

After 12 weeks, the scientists observed lymphatic vessels growing at the outer edges of the tumors in all the mice. The tumors with higher levels of VEGF-C also developed an extensive system of lymphatic vessels within the tumors. Some of these lymph vessels connected to other vessels outside the tumor and contained tumor cells. When researchers examined the lymph nodes and lungs, they found a much greater number of cancer cells in the mice with the highest production of VEGF-C. The more lymphatic vessels within the tumors, the greater the spread of cancer cells to the lymph nodes and, from there, to the lungs.

Detmar believes the correlation between lymphatic vessels and metastasis could help doctors predict when a cancer is likely to spread and, thus, which patients need especially intensive treatment. "We may be able to obtain a breast cancer specimen from a patient and measure the density of lymph vessels to predict the person's risk of metastasis, which can help us to determine treatment," he says.

Future research might also discover ways to stop the growth of lymphatic vessels in tumors by blocking the action of VEGF-C. Slowing the production of lymph vessels in the tumor might stop cancer cells from spreading via the lymph system.

Other groups of researchers have previously shown that there are several types of VEGF. Unlike VEGF-C, which promotes growth of lymphatic vessels (lymphangiogenesis), some other forms of VEGF stimulate growth of blood vessels (angiogenesis), which nourish the cancer's cells. Several drugs that block growth of blood vessels are already being tested in clinical trials, and some have shown encouraging results in patients with several types of cancers.

Since many forms of cancer produce VEGF-C, it seems likely that this study's results regarding breast cancer would also apply to other cancer types. But Debbie Saslow, PhD, director of breast and cervical cancer for the American Cancer Society, points out that what works on mice may not necessarily carry over to human patients. "This report answers some important questions concerning tumor lymphangiogenesis and metastasis," she says. "But it's a long way from any potential clinical use. No one knows how long it will take for researchers to apply these findings' to cancer patients."