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Role of Inflammation and Insulin Resistance in Mouse Models of Breast Cancer
Final rept. 15 Mar 2011-14 Mar 2013
CALIFORNIA UNIV SAN DIEGO LA JOLLA
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We have shown that obesity increases tumor burden without significantly altering tumor morphology suggesting that the primary effect of obesity is on tumor cell proliferation. Interestingly, the origin of the obesity did not have an effect as genetic obesity due to leptin mutation or diet-induced obesity due to a high fat western diet equivalently increased tumor growth. While there was no difference in macrophage infiltration into the tumors themselves, we found a significant increase in the proinflammatory M1 macrophage population in the obese mammary fat pad. Consistent with this increase, we observed increased expression of TNF- alpha in the fat pad and we subsequently showed that TNF- alpha enhances tumor cell proliferation in vitro. Thus our results point to the ability of obesity to create a microenvironment that is conducive to tumor growth rather than an effect of obesity on the tumor per se. Further studies are likely to reveal the mechanisms underlying the increased risk for breast cancer in postmenopausal women and identify potential targets for therapy.
APPROVED FOR PUBLIC RELEASE