4.5 Article

Role of HGF in obesity-associated tumorigenesis: C3(1)-TAg mice as a model for human basal-like breast cancer

期刊

BREAST CANCER RESEARCH AND TREATMENT
卷 142, 期 3, 页码 489-503

出版社

SPRINGER
DOI: 10.1007/s10549-013-2741-5

关键词

Basal-like breast cancer; Tumor latency; Microenvironment; Normal mammary gland; High fat diet-induced obesity; Fibroblast

类别

资金

  1. University Cancer Research Fund
  2. Breast Cancer and the Environment Research Program (BCERP) from the National Institute of Environmental Health Sciences (NIEHS) [U01ES019472]
  3. National Cancer Institute (NCI), NIH, DHHS
  4. UNC University Cancer Research Fund
  5. NIH [AA017376, ES019472, RO1-CA138255, DK034987, DK056350]
  6. NIH-Nutrition Obesity Research Consortium (NORC) [P30DK056350]
  7. NIH Center for GI Biology and Disease [P30DK034987]
  8. NCI Breast SPORE Program [P50-CA58223-09A1]
  9. [RO1-CA148761]

向作者/读者索取更多资源

Obesity is associated with basal-like breast cancer (BBC), an aggressive breast cancer subtype. The objective of this study was to determine whether obesity promotes BBC onset in adulthood and to evaluate the role of stromal-epithelial interactions in obesity-associated tumorigenesis. We hypothesized that hepatocyte growth factor (HGF) plays a promoting role in BBC, which express the HGF receptor, c-Met. In C3(1)-T-Ag mice, a murine model of BBC, we demonstrated that obesity leads to a significant increase in HGF secretion and an associated decrease in tumor latency. By immunohistochemical analysis, normal mammary gland exhibited obesity-induced HGF, c-Met and phospho-c-Met, indicating that the activation of the cascade was obesity-driven. HGF secretion was also increased from primary mammary fibroblasts isolated from normal mammary glands and tumors of obese mice compared to lean. These results demonstrate that obesity-induced elevation of HGF expression is a stable phenotype, maintained after several passages, and after removal of dietary stimulation. Conditioned media from primary tumor fibroblasts from obese mice drove tumor cell proliferation. In co-culture, neutralization of secreted HGF blunted tumor cell migration, further linking obesity-mediated HGF-dependent effects to in vitro measures of tumor aggressiveness. In sum, these results demonstrate that HGF/c-Met plays an important role in obesity-associated carcinogenesis. Understanding the effects of obesity on risk and progression is important given that epidemiologic studies imply a portion of BBC could be eliminated by reducing obesity.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据