Losing weight can lower levels of some proteins linked to tumor growth

Bottom Line: Overweight and obese women who lost weight through diet and exercise lowered the levels of certain proteins in their blood that play a role in angiogenesis, the process of blood vessel growth that can promote the growth and survival of cancer cells.

Journal in Which the Study was Published: Cancer Research, a journal of the American Association for Cancer Research

Author: Catherine Duggan, PhD, principal staff scientist in the Public Health Sciences Division at the Fred Hutchinson Cancer Research Center in Seattle, Washington.

Background: Angiogenesis is a vital function where new blood vessels are formed, for example, during wound healing, Duggan explained. Unfortunately, an important part of tumor growth and development is also dependent on having a supply of blood vessels to deliver nutrients and oxygen to allow a tumor to continue to grow. Some researchers have proposed that "angioprevention," that is, preventing tumor cell growth by preventing angiogenesis, might be an important strategy for cancer prevention in healthy people, but drugs that block this process have potential adverse effects, which is a deterrent to using them for cancer prevention, she said.

How the Study Was Conducted: Duggan, senior author of the study Anne McTiernan, MD, PhD, and colleagues randomly assigned 439 overweight/obese, healthy, sedentary postmenopausal women, aged 50 to 75, to one of the four study arms to measure the effect of exercise and diet on the circulating levels of proteins related to angiogenesis after 12 months.

The four arms were: a caloric restriction diet arm in which women restricted their calorie intake to no more than 2,000 kcal per day that included less than 30 percent of fat calories; an aerobic exercise arm in which women performed 45 minutes of moderate to vigorous exercise five days a week; a combined diet+exercise arm; and a control arm (no intervention).

Blood samples were collected at baseline and at 12 months.

Results: After adjusting the data for body-mass index, age, and race/ethnicity, the researchers found that after 12 months of intervention, on an average, women in the diet arm, exercise arm, and diet+exercise arm had lost 8.5, 2.4, and 10.8, percent of body weight, respectively, which were significantly higher than the average weight loss for women in the control arm (0.8 percent).

After 12 months, compared with women in the control arm, those in the diet arm and the diet+exercise arm had significantly lower levels of the angiogenesis-related proteins, but such effects were not apparent in those in the exercise-only arm. The researchers also observed a linear trend in the reductions, meaning that the more weight loss the women had, the greater the reductions in their blood angiogenesis-related protein levels.

The proteins studied include VEGF, PAI-1, and PEDF.

Author Comment: "We know that being overweight and having a sedentary lifestyle is associated with an increase in risk for developing certain types of cancer. However, we don't know exactly why," said Duggan. "We wanted to investigate how levels of some biomarkers associated with angiogenesis were altered when overweight, sedentary, postmenopausal women enrolled in a research study lost weight and/or became physically active over the course of a year."

"Our study shows that weight loss is a safe and effective method of improving the angiogenic profile in healthy individuals. We were surprised by the magnitude of change in these biomarkers with weight loss," Duggan said.

"While we can't say for certain that reducing the circulating levels of angiogenic factors through weight loss would impact the growth of tumors, it is possible that they might be associated with a less favorable milieu for tumor growth and proliferation," Duggan noted.

"Exercise is important for helping to prevent weight gain, and to maintain weight loss, but does not cause a large amount of weight loss on its own," Duggan noted. "Our study shows that making lifestyle changes--in this case simple changes to the diet to reduce weight--can lower the risk factors for cancer."

Limitations: The researchers only measured three angiogenic factors while there are several others. Also, the biomarkers were measured only in circulating blood and not in adipose or other tissues, Duggan said.