Physical change in the consistency of breast tissue may explain why obese women have a higher risk of breast cancer.
Researchers found evidence in mice and women that obesity leads to a stiffening of a meshwork of material that surrounds fat cells in the breast, called the extracellular matrix, and these biomechanical changes create the right conditions for tumor growth.
These images reveal curly collagen fibers in normal weight mice (left), but a stiffer meshwork of straight fibers in obese animals. Collagen fibers are labeled magenta, and adipocytes (fat) and inflammatory cells are green. (Credit: Fischbach Lab)
The findings, published in Science Translational Medicine, suggest clinicians may need to employ finer-scale imaging techniques in mammograms, especially for obese women, to detect a denser extracellular matrix. Also, the results should caution doctors against using certain fat cells from obese women in plastic and reconstructive breast surgeries, as these cells can promote recurring breast cancer.
“We all know that obesity is bad; the metabolism changes and hormones change, so when looking for links to breast cancer, researchers almost exclusively have focused on the biochemical changes happening. But what these findings show is that there are also biophysical changes that are important,” says Claudia Fischbach, associate professor of biomedical engineering at Cornell University.
Scarring without an injury
Fat tissue in obese women has more cells called myofibroblasts, compared with fat tissue in normal-weight women. Myofibroblasts are wound-healing cells that determine whether a scar will form. All cells secrete compounds to create an extracellular matrix, and they remodel and grab onto this meshwork to make tissue.
But when myofibroblasts make an extracellular matrix, they pull together—the action needed to close a wound—stiffening the tissue.
But “these are cells in our body regardless of injury,” says Fischbach. In obese women, there are more myofibroblasts than in lean women, which leads to scarring and stiffening without an injury in the extracellular matrix. Tumors also recruit more myofibroblasts than are found in healthy tissue, which also leads to stiffer extracellular matrix.
Fischbach and colleagues studied obese mice and found scarred and stiffer extracellular matrices in the absence of tumors. They also examined tumor-free human breast tissues and found the same pattern of stiffness in the matrices of obese women compared with normal-weight women.
Fat tissue is made up of adipose (fat) cells and adipose stromal cells that also contain myofibroblasts. The researchers isolated adipose stromal cells from the breasts of lean and obese mice and used these cells to make matrices. When tumor cells were added onto the matrix from the obese cells, they grew. Through experiments, the researchers proved the stiffness of this matrix changed a cell’s behavior and promoted tumor growth.
They also found that when calories were restricted in obese mice, scarring and stiffening in the matrix of their mammary fat decreased, suggesting a possible therapy for obesity-related cancer.
Many obese women get regular mammograms but signs of disease don’t show up because detecting their dense extracellular matrix between the fat cells requires a finer-scale resolution. The findings “may inspire use of higher resolution imaging techniques to detect those changes,” says Fischbach. “Right now, people don’t look for [stiffer extracellular matrices] as a clinical biomarker.”
During plastic or reconstructive surgery following mastectomy in breast cancer patients, doctors may inject adipose stromal cells from obese donors to regenerate tissue. “What our data suggests is that it is really important where these cells are being taken from,” Fischbach says. “If you use these cells from an obese patient, they are very different and you may actually be driving malignancies if you implant them.”
The National Institutes of Health, the National Science Foundation, the Breast Cancer Research Foundation, and the Botwinick-Wolfensohn Foundation at Weill Cornell Medical College funded the study.
This text is published here under a Creative Commons License.
Author: Krishna Ramanujan-Cornell University
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