Having established that excessive fat tissue can fuel the growth of certain cancers, researchers have turned their attention to the molecular mechanisms involved in the process in the hopes of developing new cancer treatments.
The discovery of an on/off switch for a common obesity-associated malignancy could aid those efforts, report scientists from The University of Texas Health Science Center at Houston (UTHealth) and The University of Texas MD Anderson Cancer Center in the journal Nature Communications.
“Some tumors rely on fat to grow aggressively,” said Mikhail Kolonin, Ph.D., senior author and associate professor at John P. and Kathrine G. McGovern Medical School at UTHealth. “We’ve discovered a molecular network without which fat no longer promotes tumor growth.”
The researchers focused on prostate cancer, which claims more than 26,000 lives in the United States each year. Other obesity-associated malignancies include breast and colorectal cancer.
The obesity-induced switch identified in the study is chemokine CXCL1, a signaling molecule that regulates cell trafficking. When the investigators blocked the switch in mouse models, the obesity-induced progression of prostate cancer slowed.
To see if their findings apply to humans, the investigators compared the CXCL1 levels in the tumors of patients with prostate cancer and obesity to those with prostate cancer and no obesity. The CXCL1 signaling to adipose tissue was found to be higher in the obese patients.
When activated in excessive fat, CXCL1 sends out a signal that attracts cells from fat to the tumor, Kolonin said. These particular fat cells are called adipose stromal cells (ASC) and they support tumor-nourishing blood vessels.
“As the prevalence of obesity is rising, insights into the mechanisms underlying its link with cancer aggressiveness are urgently needed to develop new strategies for reducing prostate cancer morbidity and mortality,” the authors wrote.
Kolonin’s group had previously used animal models to suppress obesity-associated cancer by using an experimental drug depleting ASC. “We’re exploring multiple ASC-targeting strategies,” Kolonin said. “Blockade of CXCL1 function to recruit ASC to tumors could be developed to intervene in cancer progression.”
