Study Shows Fat Tissue Influences Tumor Growth Despite Diet

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Overweight cancer patients generally have a worse prognosis compared to their leaner counterparts. A new study published today in Cancer Research suggests a mechanism for the link between obesity and cancer.

Overweight cancer patients generally have a worse prognosis compared to their leaner counterparts. A new study published today in Cancer Research suggests a mechanism for the link between obesity and cancer.

“Our study for the first times proves that excess fat tissue can directly promote cancer progression irrespective of the diet responsible for obesity onset,” said Mikhail Kolonin, PhD, an associate professor at the Institute of Molecular Medicine at the University of Texas Health Science Center, Houston, and lead author of the study.

“Epidemiological studies have revealed the association between obesity and increased progression of a number of cancers,” said Kolonin. “Because obesity is caused by overgrowth of white fat tissue, it was logical to test its direct role in cancer progression.”

While cytokines secreted by fat tissue, called adipokines, have been suggested to be responsible for the obesity–cancer link, Kolonin and his team had another theory. “We hypothesized that fat tissue starts to serve as a source of an increased number of adipose stromal cells which fuels cancer progression through paracrine secretion of factors within the tumor.” Unlike endocrine signaling, paracrine signaling occurs in close proximity rather than relying on the blood stream to carry the signaling factor long distances.

The hypothesis was based on research from both Kolonin’s laboratory and that of other groups suggesting fat tissue transplanted into animals is capable of trafficking to tumors to promote their growth. This previous research suggested that fat tissue itself, rather than fat intake through diet can influence tumor growth.

The researchers normalized the diet of both lean and obese mice for one month prior to grafting tumor cells on the mice. The obese mice had faster growing tumors compared to the lean mice that were fed the same diet. Obese mice had more adipose stromal tissue compared to lean mice, and this tissue was better mobilized by the tumor into circulation. The stromal fat progenitor cells were found to incorporate into the tumor as either fat cells or as tumor-associated blood vessels. “Our study identifies stromal adipocyte progenitors as a migratory population of cells that are expanded in diet-induced obesity and are recruited to shape the tumor microenvironment,” said Kolonin. The experiments also provide evidence that fat stromal progenitor cells can support tumor vasculature.

This mouse model data, according to Kolonin, is consistent with the observation that both obese individuals and cancer patients have adipose progenitor cells in their circulating blood.

Next Steps

“We are actively working on elucidating the underlying molecular mechanisms,” said Kolonin. “It is possible that this response to tumor signals is not specific for adipose stromal cells, but is rather a general feature of mesenchymal stromal cells. However, our previous reports indicate that stromal cells from adipose tissue have a distinct capacity to promote tumor growth.”

Kolonin and colleagues are currently working on targeting and depleting adipose progenitor cells. “Clinical studies have shown that anti-obesity interventions reduce cancer risk, which makes this direction of our research potentially relevant for possible future strategies to cancer prevention,” said Kolonin.

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