Weight loss prevents obesity-associated basal-like breast cancer progression: Role of hepatocyte growth factor
Sundaram S, Le T, Essaid L, Freemerman AJ, McNaughton KK, Bendt KM, Darr DB, Troester MA, Makowski, L.
Frontiers in Oncology 4:175. doi: 10.3389/fonc.2014.00175. PMID pending
Lay Abstract
Population studies suggest that obesity contributes to at least half of an aggressive subtype of breast cancer called basal-like breast cancer (BBC). Obesity is widespread and is one of the few risk factors for breast cancer that we may be able to control. We previously showed that obesity in adult mice drove early onset of BBC tumors which was similar to findings that in humans, BBC often strikes at a young age. In our study, obesity also drove the increase in tumor growth factors including the hepatocyte growth factor (HGF) and its receptor, c-Met in the mammary gland. Thus, we discovered a link between the cancer causing HGF/c-Met pathway and BBC in obesity. Various studies in human populations have suggested therefore that lifestyle intervention including weight loss could prevent a large proportion of BBC. Hence our intention was to better understand if weight loss could lead to decreased tumor growth in mice and to discover the molecular mechanisms associated with obesity and weight loss with the overall goal to prevent or treat BBC. In mice made obese from feeding a high fat diet from an early age, tumors grew rapidly compared to mice that remained lean throughout life. When obese mice were induced to lose weight before tumors developed, tumor growth was slowed to levels similar to lean mice. Proteins that can lead to increased cancer onset and growth were increased by obesity and importantly, decreased with weight loss including the HGF/c-Met pathway, insulin, and the leptin:adiponectin ratio. Our findings suggest that obesity-driven factors such as HGF/cMet, insulin, and the leptin: adiponectin ratio may contribute to the onset of obesity-promoted BBCs and the dramatic reversal of obesity-driven tumor aggressiveness after weight loss. Studies to discover if BBC can be prevented or treated through using drugs to inhibit the HGF pathway are currently ongoing. Taken together, our data demonstrate that obesity-increased tumor growth can be reversed by weight loss even before tumors were detected. Our findings are encouraging and further support maintaining a healthy weight to decrease cancer risk.
Link to press release: sph.unc.edu/sph-news/study-in-mice-finds-weight-loss-reduces-progression-of-basal-like-breast-cancer/ |
