Fat Cells Could Block Chemotherapy Drugs

One more reason to beware of obesity. It could impair the immune system's ability to stop cancer, or predispose cells to become cancerous, US researchers say.

An article in the September 22, 2009, issue of the journal Cancer Research highlights the role of the fat cell in fostering leukemia chemotherapy resistance, and, according to the senior author, Steven D. Mittelman, “…may help explain the increased leukemia relapse rate in obese children and adults.”

An earlier study had found that obese children diagnosed with leukemia had a 50-percent higher chance of relapsing than lean children.

To investigate the causes, Dr. Mittelman worked with Nora Heisterkamp, also in the Division of Hematology-Oncology at Childrens Hospital and an expert in leukemia cell biology.

“We found that some leukemia cells were ‘hiding out’ in the fat tissue during chemotherapy,” Dr. Mittelman said.  “To figure out whether the fat cells were allowing the leukemia to avoid the chemotherapy, we cultured fat and leukemia cells together.  When we treated the leukemia cells with the many traditional chemotherapy drugs used in children with leukemia, they each worked less effectively when the leukemia cells had fat cells nearby.” 

 “The fat cells seem to produce survival signals for the leukemia cells,” said first author James Behan, a medical student at USC’s Keck School of Medicine, “…which prevent the leukemia cells from entering apoptosis, or programmed cell death.”

Dr. Mittelman and his colleagues at The Saban Research Institute of Childrens Hospital Los Angeles and USC’s Keck School of Medicine concluded that the fat cells somehow protect leukemia cells from chemotherapy.  And since obese children have more, larger fat cells than thin kids, that might be the reason for the poorer prognosis seen in obese patients.

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Dr. Mittelman added, “Leukemia is the most common cancer in children, so it is important that we understand what causes some children to relapse.  Also, given the growing prevalence of obesity worldwide, these effects are likely to have increasing importance to cancer treatment.”

David Hockenbery, member of the Fred Hutchinson Cancer Research Center and professor or internal medicine at the University of Washington, said, “This study provides striking experimental support for the clinical observations that obesity is associated with poor prognosis in multiple cancer.

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“In addition, by highlighting a potential communication between adipocyte and leukemia cells, this research will stimulate efforts to find a diffusible factor that protects leukemia cells from chemotherapy,” Dr. Hockenbery said.

The research was supported by grants from the National Institutes of Health and the National Cancer Institute’s Centers for Transdisciplinary Research on Energetics and Cancer.



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