Editors' ChoiceCancer

Fat fibrosis and breast cancer

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Sci. Signal.  25 Aug 2015:
Vol. 8, Issue 391, pp. ec240
DOI: 10.1126/scisignal.aad2815

One of the many risk factors for cancer is obesity—but why? Seo et al. examined the cellular, structural, and molecular changes that happen in breast tissue in obese animals and people. They found that obesity induces fibrotic remodeling of the mammary fat pad, leading to changes in extracellular matrix (ECM) mechanical properties, via myofibroblasts and adipose stem cells (ASCs), regardless of ovary function. Through altered mechanotransduction, ECM from obese mice promoted human breast cancer cell growth, as well as the growth of premalignant breast cells (those that have yet to become cancerous). Tissues from obese patients revealed more severe fibrotic remodeling around tumors and higher levels of a key mechanosignaling component, YAP/TAZ, than their lean counterparts. The authors further demonstrated that caloric restriction in obese mice decreased fibrosis in mammary fat, suggesting a therapeutic angle for obesity-related cancers. By linking tumorigenesis to the behavior of fat cells and ECM mechanics, the authors point toward new drug targets for preventing cancer progression (see also Arendt and Kuperwasser). However, a cautionary tale also exists in the use of adipose tissue and cells for patients after mastectomy, as ASCs from obese individuals may have the capacity to promote breast cancer recurrence.

B. R. Seo, P. Bhardwaj, S. Choi, J. Gonzalez, R. C. Andresen Eguiluz, K. Wang, S. Mohanan, P. G. Morris, B. Du, X. K. Zhou, L. T. Vahdat, A. Verma, O. Elemento, C. A. Hudis, R. M. Williams, D. Gourdon, A. J. Dannenberg, C. Fischbach, Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis. Sci. Transl. Med. 7, 301ra130 (2015). [Abstract]

L. M. Arendt, C. Kuperwasser, Working stiff: How obesity boosts cancer risk. Sci. Transl. Med. 7, 301fs34 (2015). [Abstract]