Equivalent of 2-4 drinks daily fuels blood vessel growth, encourages cancer tumors in mice

The research provides the first mammalian model of the links between alcohol, VEGF, and tumor growth, said Wei Tan, the study’s lead author. The study increases understanding of how alcohol over-stimulates production of vascular endothelial growth factor (VEGF) — a substance that the body needs, but which can be harmful when there is too much of it.

The new mouse model could lead to a way to block VEGF over-production, a step that could reduce the incidence of cancer and has important implications for cancer education and prevention. Wei Tan, Megan Shparago, Amelia P. Bailey and Jian-Wei Gu of the University of Mississippi Medical Center will present "Moderate alcohol intake stimulates tumor angiogenesis and expression of vascular endothelial growth factor (VEGF) in a mouse model," at the Experimental Biology Conference 2006, April 1-5 in San Francisco.

The study earned Tan a Caroline tum Suden/Frances A. Hellebrandt Professional Opportunity Award from the American Physiological Society (APS) for exemplary research. The presentation was part of the scientific program sponsored by APS.

*Paper presentation: "Moderate alcohol intake stimulates tumor angiogenesis and expression of vascular endothelial growth factor (VEGF) in a mouse model," 12:45 p.m. – 3 p.m. Monday April 3, Angiogenesis and Vascular Growth, 462.3 /board # C264. On view 7:30 a.m. to 6 p.m., Convention Center Exhibit Hall. Research was by Wei Tan, Megan Shparago, Amelia P. Bailey and Jian-Wei Gu of the Department of Physiology, University of Mississippi Medical Center, Jackson, MS.

Researchers develop mouse model

Unlike studies which use alcohol that would be the equivalent of high consumption in humans, the researchers gave mice a more moderate dose — the equivalent to 2-4 glasses of alcohol per day.

Six male mice received 1% alcohol in their drinking water for eight hours each night during the four-week experiment, Tan said. The six mice in the control group received plain water. In the second week, the researchers injected the mice, both experimental and controls, with mouse melanoma. They ended the experiment after four weeks.

According to Tan, the tumors of the mice that ingested alcohol:

• were nearly twice as heavy compared to the mice that did not have alcohol
• showed a dramatic increase in new micro-vessels, that is, blood vessels that cannot be seen with the naked eye, such as capillaries
• were nearly twice as dense with blood vessels
• showed a significant increase in VEGF

Alcohol long identified as cancer risk "It’s very important to have a model of how to prevent cancer," and this study provides that model, Gu said. "Epidemiologists have recognized alcohol as a risk factor for cancer for 100 years," but this study examines how that happens.

The mouse study builds on an earlier study with chicks that showed alcohol consumption increased the expression of a protein known as VEGF. VEGF fuels tumor growth by spurring the development of blood vessels in cancer cells that might otherwise die.

Normally, the immune system can kill off small tumors. However, when they grow large enough the body can no longer fight off the tumor cells. This is why angiogenesis is so important, Gu said.

VEGF, a protein that stimulates formation of blood vessels, helps organ tissues grow. Unfortunately, it also aids tumors grow by helping them develop a system of blood vessels. Without these blood vessels, cancer cells that form small tumors would quickly die.

The vast majority of tumors result from over expressed VEGF, Gu explained. "Every day, we produce a lot of cancer cells, but they don’t become bigger," he said. But if the cell establishes blood vessels, the tumor grows and strengthens, a process known as angiogenesis.

Cells dislike alcohol

When alcohol is consumed, it enters the cells, which attempt to eliminate it. Because it is difficult to break it down, the cells must increase metabolic activity to do that, Tan explained. But that requires oxygen, and the cells may deplete themselves of oxygen in an attempt to break down the alcohol.

This oxygen-depletion, known as hypoxia, indirectly induces production of VEGF. VEGF, in turn, stimulates the growth of new blood vessels to meet the increased oxygen demand. It is still too early to define safe levels of alcohol consumption in humans, Tan said, but she advises caution when drinking, particularly for individuals who drink every day.

"If you have risk for any kind of cancer, don’t drink at all," Gu advised. For those not at risk, the occasional social drink is fine, but "I don’t think 2-4 drinks per day is okay," Gu ventured. The public needs to know of these results as a tool of cancer prevention. Gu was once approached by a man on chemotherapy who asked him if it was okay to drink. The answer was a firm "no."