PMID- 26132316 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150703 LR - 20220331 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 7 IP - 3 DP - 2015 Jun 26 TI - High-Fat, High-Calorie Diet Enhances Mammary Carcinogenesis and Local Inflammation in MMTV-PyMT Mouse Model of Breast Cancer. PG - 1125-42 LID - 10.3390/cancers7030828 [doi] AB - Epidemiological studies provide strong evidence that obesity and the associated adipose tissue inflammation are risk factors for breast cancer; however, the molecular mechanisms are poorly understood. We evaluated the effect of a high-fat/high-calorie diet on mammary carcinogenesis in the immunocompetent MMTV-PyMT murine model. Four-week old female mice (20/group) were randomized to receive either a high-fat (HF; 60% kcal as fat) or a low-fat (LF; 16% kcal) diet for eight weeks. Body weights were determined, and tumor volumes measured by ultrasound, each week. At necropsy, the tumors and abdominal visceral fat were weighed and plasma collected. The primary mammary tumors, adjacent mammary fat, and lungs were preserved for histological and immunohistochemical examination and quantification of infiltrating macrophages, crown-like structure (CLS) formation, and microvessel density. The body weight gains, visceral fat weights, the primary mammary tumor growth rates and terminal weights, were all significantly greater in the HF-fed mice. Adipose tissue inflammation in the HF group was indicated by hepatic steatosis, pronounced macrophage infiltration and CLS formation, and elevations in plasma monocyte chemoattractant protein-1 (MCP-1), leptin and proinflammatory cytokine concentrations. HF intake was also associated with higher tumor-associated microvascular density and the proangiogenic factor MCP-1. This study provides preclinical evidence in a spontaneous model of breast cancer that mammary adipose tissue inflammation induced by diet, enhances the recruitment of macrophages and increases tumor vascular density suggesting a role for obesity in creating a microenvironment favorable for angiogenesis in the progression of breast cancer. FAU - Cowen, Sarah AU - Cowen S AD - Department of Surgery, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. scowen@miis.edu. AD - Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. scowen@miis.edu. FAU - McLaughlin, Sarah L AU - McLaughlin SL AD - Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. smclaughlin@hsc.wvu.edu. FAU - Hobbs, Gerald AU - Hobbs G AD - Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. ghobbs@stat.wvu.edu. AD - Department of Statistics, West Virginia University, Morgantown, WV 26506, USA. ghobbs@stat.wvu.edu. FAU - Coad, James AU - Coad J AD - Department of Pathology, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. jcoad@hsc.wvu.edu. FAU - Martin, Karen H AU - Martin KH AD - Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. kamartin@hsc.wvu.edu. AD - Department of Neurobiology and Anatomy, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. kamartin@hsc.wvu.edu. FAU - Olfert, I Mark AU - Olfert IM AD - Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. imolfert@hsc.wvu.edu. AD - Department of Human Performance and Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. imolfert@hsc.wvu.edu. FAU - Vona-Davis, Linda AU - Vona-Davis L AD - Department of Surgery, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. lvdavis@hsc.wvu.edu. AD - Mary Babb Randolph Cancer Center, West Virginia University Health Sciences Center, Morgantown, WV 26506, USA. lvdavis@hsc.wvu.edu. LA - eng GR - P20 RR016440/RR/NCRR NIH HHS/United States GR - P30 RR032138/RR/NCRR NIH HHS/United States GR - U54 GM104942/GM/NIGMS NIH HHS/United States GR - P20 RR016477/RR/NCRR NIH HHS/United States GR - S10 RR026378/RR/NCRR NIH HHS/United States GR - P20 GM103434/GM/NIGMS NIH HHS/United States GR - P30 GM103488/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20150626 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC4586761 OTO - NOTNLM OT - angiogenesis OT - high-fat diet OT - inflammation OT - obesity OT - tumor progression EDAT- 2015/07/02 06:00 MHDA- 2015/07/02 06:01 PMCR- 2015/06/26 CRDT- 2015/07/02 06:00 PHST- 2015/05/15 00:00 [received] PHST- 2015/06/16 00:00 [revised] PHST- 2015/06/18 00:00 [accepted] PHST- 2015/07/02 06:00 [entrez] PHST- 2015/07/02 06:00 [pubmed] PHST- 2015/07/02 06:01 [medline] PHST- 2015/06/26 00:00 [pmc-release] AID - cancers7030828 [pii] AID - cancers-07-00828 [pii] AID - 10.3390/cancers7030828 [doi] PST - epublish SO - Cancers (Basel). 2015 Jun 26;7(3):1125-42. doi: 10.3390/cancers7030828.