Inflammation-associated cancers of the colon, prostate, and breast have increased dramatically during the past 30 years in Westernized countries resulting in a public health crisis. Concomitantly, health advancements including sterile births and widespread use of antibiotics have led to increasingly hygienic living conditions. We speculate that modernized living practices contribute to gastrointestinal (GI) tract imbalances, which in turn result in inflammatory disorders - such as allergy and asthma - and later in life, inflammation-associated cancers. We have already shown in mouse models that GI tract bacteria modulate growth of cancer in extra-intestinal tissues such as mammary and prostate glands. Here, we aim to understand interactions between GI tract microbiome and breast tumor stromal cells. Partnered with parent U54 grant of Timothy C Wang, MD, this collaborative U01 will build upon our earlier findings relating to breast cancer development. We propose a combination of high-throughput immunology, microbiome analyses and gnotobiotic mouse technologies to elucidate specific mechanisms. We have assembled a world-class team of scientists and physicians uniquely poised to carry out this multi-disciplinary research. We predict that remedies to restore GI tract immune balance will be an effective and practical approach to prevent and treat extra-intestinal malignancies such as breast cancer.
Chronic inflammation increases risk of cancer in humans and in mice. Environmental exposures appear to modulate breast cancer in women but inflammatory mechanisms are not well understood. We have shown in mice that gut bacteria modulate mammary tumors. We propose here to test bowel microbes and inflammatory cells in women and mice with ultimate translational goals to abolish breast cancer.
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|Ericksen, Russell E; Rose, Shannon; Westphalen, Christoph Benedikt et al. (2014) Obesity accelerates Helicobacter felis-induced gastric carcinogenesis by enhancing immature myeloid cell trafficking and TH17 response. Gut 63:385-94|
|Poutahidis, Theofilos; Kleinewietfeld, Markus; Erdman, Susan E (2014) Gut microbiota and the paradox of cancer immunotherapy. Front Immunol 5:157|
|Lakritz, Jessica R; Poutahidis, Theofilos; Levkovich, Tatiana et al. (2014) Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice. Int J Cancer 135:529-40|
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