Researchers find that increase in leptin may promote colorectal neoplasms

Jul 21 2010

While researchers have known that obesity increases the risk for the development of colon cancer, the underlying molecular mechanisms have remained unclear.

Now, for the first time, a collaborative study of researchers at the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University's College of Science and Technology and the Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy have found that an increase in leptin, a cytokine that is normally increased in obese or overweight individuals, may promote colorectal neoplasms by activating colorectal cancer stem cells. Their findings appear in the journal, Endrocrine-Related Cancer (http://erc.endocrinology-journals.org/cgi/content/abstract/ERC-10-0083v1).

Cancer stem cells constitute a small subfraction of tumor cells that are characterized by long lifespan and capacity for self-renewal, and are responsible for tumor development, resistance to treatments and cancer recurrence. In colon cancer, leptin is able to increase the growth, survival, and resistance to certain chemotherapy treatments in this key cell population.
Leptin, a fat tissue-derived pluripotent cytokine regulating appetite and energy balance in the brain, also controls many physiological and pathological processes in peripheral organs, including carcinogenesis.

Colon cancer has increased in developed countries, possibly due to sedentary lifestyles and high caloric diets. Prior research has linked obesity to colorectal cancer risk by .4-1.0 fold in men and up to 2.0 fold in premenopausal women.

"Since targeting cancer stem cells may be a translationally relevant strategy to improve clinical outcomes, interfering with leptin signaling by targeting leptin receptors might become a novel attractive option for colorectal cancer treatment, particularly in obese patients," says senior author of the study, Eva Surmacz, Ph.D., Associate Professor in Biology at Temple University and Director of the Obesity and Cancer Program at the Sbarro Institute.

"It is important to consider that cancer stem cells have been identified in several human malignancies," says Monica Bartucci, a collaborator of Professor Surmacz at Thomas Jefferson University who is now employed by the Istituto Superiore di Sanità in Rome. "Understanding how cancer stem cells interact with a tumor environment, including hormones like leptin, is likely to have significant implications for treatment management of different cancer types in human patients. We hope, in collaboration with Dr. Surmacz, not only to test the effects of leptin antagonist compounds on colon cancer stem cells but also to study the results of leptin stimulation on cancer stem cells isolated in other cancer tissues."