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Obesity deteriorates DMBA‐induced tumorigenesis in vitro and in vivo
Author(s) -
Hsieh ChiaChien,
Peng ShihHan,
Chou MeiJia
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.790.26
Subject(s) - dmba , adipose tissue , medicine , endocrinology , angiogenesis , adipocyte , in vivo , mammary tumor , stromal cell , carcinogenesis , carcinogen , leptin , white adipose tissue , breast cancer , chemistry , cancer research , cancer , biology , obesity , microbiology and biotechnology , organic chemistry
Obesity and overweight are associated to several chronic diseases. Growing body of evidence showed extra adiposity influences multiple cancers progression, such as breast cancer. During the adiposity, macrophages infiltrate into the adipose tissue and accompany inflammatory mediators secretion fertilized a microenvironment that is favorable for neoplastic cells. The aim of this study is to investigate whether obesity correlate to mammary tumor development in vitro and in vivo . In vitro study, the obese‐related mediators, such as leptin and 3T3‐L1 adipocyte conditioned medium, enhanced cancerous foci formation inducted by environmental chemical carcinogen, 7,12‐Dimethylbenz [a] anthracene (DMBA) in fibroblast NIH/3T3 cells. In vivo study, C57BL/6J female mice fed low fat (LF), and high fat (HF) experimental diets, and some of them were oral gavage DMBA to induce breast cancer, as LF+DMBA (LFD), and HF+DMBA (HFD). The results indicated that breast cancer incidence was about 20% in HFD group with 169 mg tumor weight and 14% in LFD group with 77 mg tumor weight, and HFD mice have significantly lower body weight compared to the HF mice. The section of mammary tumor from HFD mice accompanied stromal invasion, morphological aggressiveness and multiple cells infiltration, and showed apparently proliferative marker Ki67, endothelial marker CD31 and macrophage marker F4/80 expressions compared to that in LFD group. The section of epididymal adipose tissue from the DMBA groups showed more macrophage infiltration and these cells polarized to M1 with higher CD11c expression compared to the mice fed the same diet. In addition, the adipose sections from HF groups have lower M2 macrophages accumulation. In summary, obese mediators enhanced cancerous foci formation by DMBA challenge in vitro , and high fat diet caused neoplastic aggravation in mammary tumor, particularly, decreased suppressive M2 macrophages infiltration into adipose tissues in vivo . Support or Funding Information Ministry of Science and Technology, Taiwan (MOST 103‐2320‐B‐003‐003‐MY3).