Stiff cellular environment links obesity to breast cancer

Malignant human cells grow more quickly on rigid material from fat mice

Fat cells in obese mice modify nearby proteins, creating a rigid environment that increases cancer cells’ ability to grow and spread, a new study finds.

When placed on stiff extracellular material taken from obese mice, human breast cancer cells and precancerous cells grew more rapidly, scientists report August 19 in Science Translational Medicine.

Previous studies have shown that obesity increases the risk of breast cancer and worsens a patient’s prognosis. But scientists don’t have a good understanding of the processes responsible for this link, says biomedical engineer Paolo Provenzano of the University of Minnesota in Minneapolis. “This study sheds considerable light on that mechanism,” he says. “It’s further proof of principle that engineering principles are important to our understanding of cancer, and it’s not just a biochemical or genetic disease.”

Few studies analyze how obesity changes a cell’s physical environment, says study coauthor Claudia Fischbach, a biomedical engineer at Cornell University.

While fat cells make tissue “floppy,” Fischbach says, the material in between fat cells is quite stiff. Cells can sense the resistance of their surroundings, she says, and alter their behavior when confronted with a more rigid environment.

Obese mice had a greater number of cells called myofibroblasts in their fat tissue, the scientists found. These cells remodel and stiffen their surroundings. But the study’s results suggest that this obesity-induced rigidity might be reversible; a low-calorie diet reduced the number of myofibroblasts in obese mice’s breast tissue.

Fischbach and colleagues observed similar differences in humans. Breast tissue was thicker and more fibrous in obese women than in their leaner counterparts, whether this tissue was cancerous or healthy.

Provenzano says the results suggest that it might be possible to reduce the risk or progression of cancer by softening a cell’s surroundings.

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