Scientists Discover How Obesity Makes Breast Cancer Worse

We knew being morbidly overweight causes cancers, but didn't know how. Now we have a clue to mechanism, in mice at least.

Ruth Schuster
Ruth Schuster
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Breast cancer can become more serious in the obese - because, it turns out, the protein scaffolding in the matrix is more rigid.
Breast cancer can become more serious in the obese - because, it turns out, the protein scaffolding in the matrix is more rigid.Credit: C. Bickel, Science Translational Medicine
Ruth Schuster
Ruth Schuster

Obesity has been linked with a number of cancers, but science hasn't been clear why. Now at least the how is becoming clearer, in the case of breast malignancy in mice: obesity drives the disease by making the mammary fatty tissue stiffer, which in turn creates an environment that coddles tumor growth.

The correlation between breast cancer and obesity has been observed mainly, if not exclusively, in post-menopausal women who have not used hormone replacement therapy.

Cancer and obesity isn't just about incidence. Compared to patients in the normal weight range, obese individuals tend to have more advanced and aggressive breast tumors, writes the scientific team in a paper published in Science Translational Medicine today, "Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis".

But how could merely being fat cause profound change in susceptibility to cancer? The final answer, when we get it, will surely be incredibly complex, including factors such as inflammation – obese people suffer from chronic inflammation, and changes in hormone levels. Adipose tissue produces high amounts of estrogen, high levels of which have been associated with the risk of breast and certain other cancers.

Rigid protein structures

Meanwhile, studying breast fatty tissue in both human patients and mice led the team to notice that obesity changes the structure of the extracellular matrix - the space between cells. that space isn't a void: it's filled with "scaffolds" of collagen and other fibrous that hold the cells in place.

Obese mice had more relatively cells called myofibroblasts, which deposited denser, more rigid proteins into the extracellular matrix.

The scientists point out that they found the same whether the murines were naturally fat ("genetically obese") or stuffed with high-fat foods.

The empiric observation was repeated in women: obese breast cancer patients also proved to have thicker, stiffer collagen fibers than their slimmer counterparts.

How the stiffer intracellular matrix encourages tumors to grow is another question, though. It seems the mechanical changes – the more rigid support system– somehow translates into biochemical signals that encourage tumor growth. This postulation is supported by the observation that precancerous breast cells grown in extracellular matrices from obese fat tissue, compared to those from lean tissue, were more likely to turn malignant.

Dieting may help

Breast cancer isn't the only cancer risk the obese run. According to the U.S. National Institute of Health, this chronic condition of overweight is associated with several cancers, including of the digestive system - from esophagus to rectum, the lining of the uterus, the kidney, thyroid and gallbladder – and the breast. The NIH however qualifies that the elevated breast cancer risk among the obese is correlated with post-menopausal women.

How much worse is the risk for the morbidly fat? Again according to the NIH, based on a 2007 study (and there's no reason to assume the trends have changed), that year about 4% of cancer cases in men and 7% in women were due to obesity. The degree of causality is very different for different cancers but the heaviest effects were observed in endometrial cancer and esophageal adenocarcinoma.

So, can dieting help? Maybe. "Placing obese mice on a diet reduced the number of myofibroblasts in mammary tissue, hinting that weight loss can potentially reverse this tissue stiffening," writes the team reassuringly in their abstract.

By the way, it is true that Jewish women of Ashkenazi descent have a higher prevalence of mutations that increase the risk of breast and ovarian cancer, which does not mean that breast cancer is some sort of Jewish disease.



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