Study suggests how expanding waistlines may contribute to cancer

Fat progenitor cells may contribute to cancer growth by fortifying the vessels that provide needed blood to tumors, according to preclinical research findings by investigators at The University of Texas Health Science Center at Houston (UTHealth).

The results were reported in Cancer Research, a journal of the American Association for Cancer Research.

Studies of groups of people have demonstrated a link between obesity and certain cancers; however, the physiological causes have not been identified.  The World Health Organization reports that in 2008 there were more than 1.4 billion obese adults in the world and that cancer claimed the lives of 7.6 million that year.

Some researchers have theorized that what obese people eat may affect cancer progression. However, although diet is an important factor, the direct effect of excess fat tissue on tumors has to be taken into consideration, said Mikhail Kolonin, Ph.D., senior author and associate professor at the Center for Stem Cell and Regenerative Medicine at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth.

The UTHealth scientists found a new link between tumor growth and obesity. They report that tumors emit a signal that attracts progenitor cells from white adipose tissue in mouse models of cancer. These cells in turn support the network of blood vessels that nourish tumors – a process called tumor angiogenesis.

“For the first time, we have demonstrated that excess fat is a key factor in cancer progression regardless of the diet contributing to the extra weight,” Kolonin said.

“In an attempt to understand how fat tissue fuels tumor growth, our laboratory has focused on a possible role of adipose stromal progenitor cells. These cells serve as stem cells in fat tissue. We have discovered that they expand in obesity and are mobilized into the systemic circulation,” Kolonin said.

“Our experiments show that fat progenitors are recruited by tumors, where they incorporate into blood vessels and become fat cells,” said Yan Zhang, M.D., Ph.D., the study’s lead author and research scientist at the UTHealth Medical School. “We found that obese animal fat progenitor cells recruited by tumors improved vascular function and, therefore, increased survival and proliferation of cancer cells.”

Chieh Tseng, study author and graduate research assistant at the The University of Texas Graduate School of Biomedical Sciences at Houston, said, “Our work has the potential to help a lot of people. Currently, we are investigating the molecular mechanisms of fat progenitor cell homing to tumor. We are also screening for new molecules targeting the pathways through which cells traffic from fat tissue to promote tumor growth.”

“The next step in this research would be to inactivate fat progenitor cells in an effort to slow cancer progression,” said Kolonin, who is on the faculty of the graduate school and is the holder of the Jerold B. Katz Distinguished Professorship in Stem Cell Research at UTHealth.

Other UTHealth study authors include Alexes Daquinag, Ph.D., Felipe Amaya-Manzanares and Olga Sirin, Ph.D.

The study, which is titled “Stromal Progenitor Cells from Endogenous Adipose Tissue Contribute to Populations of Pericytes and Adipocytes in Tumor Microenvironment,” was supported by the Cancer Prevention & Research Institute of Texas and the American Cancer Society.

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