title: Insulin-like growth factor binding protein-3 links obesity and breast cancer progression.
abstract: Obesity is associated epidemiologically with poor breast cancer prognosis, but the mechanisms remain unclear. Since IGF binding protein-3 (IGFBP-3) influences both breast cancer growth and adipocyte maturation, it may impact on how obesity promotes breast oncogenesis. This study investigated the role of endogenous IGFBP-3 on the development of obesity and subsequently on breast tumor growth. Wild-type (WT) C57BL/6 or IGFBP-3-null (BP3KO) mice were fed a high-fat diet (HFD) or control chow-diet for 15 weeks before orthotopic injection with syngeneic EO771 murine breast cancer cells. When the largest tumor reached 1000 mm3, tissues and tumors were excised for analysis. Compared to WT, BP3KO mice showed significantly reduced weight gain and mammary fat pad mass (contralateral to tumor) in response to HFD, despite similar food intake. EO771 tumor weight and volume were increased by HFD and decreased by BP3KO. Despite differences in tumor size, tumors in BP3KO mice showed no differences from WT in the number of mitotically active (Ki67+) and apoptotic (cleaved caspase-3+) cells, but had greater infiltration of CD3+ T-cells. These data suggest that endogenous (circulating and/or stromal) IGFBP-3 is stimulatory to adipose tissue expansion and enhances mammary tumor growth in immune-competent mice, potentially by suppressing T-cell infiltration into tumors.
authors.affiliation: Hormones and Cancer Laboratories, Kolling Institute, University of Sydney, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Scully
authors.affiliation: Hormones and Cancer Laboratories, Kolling Institute, University of Sydney, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia.
authors.forename: Sue M
authors.initials: SM
authors.lastname: Firth
authors.affiliation: Hormones and Cancer Laboratories, Kolling Institute, University of Sydney, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia.
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Scott
authors.affiliation: Hormones and Cancer Laboratories, Kolling Institute, University of Sydney, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia.
authors.forename: Hasanthi C
authors.initials: HC
authors.lastname: de Silva
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, New Brunswick, NJ 08854, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Pintar
authors.affiliation: Department of Anatomy, Bosch Institute, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Tailoi
authors.initials: T
authors.lastname: Chan-Ling
authors.affiliation: Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Twigg
authors.affiliation: Hormones and Cancer Laboratories, Kolling Institute, University of Sydney, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Baxter
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000098:blood supply / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D002465:Cell Movement; D059305:Diet, High-Fat; D018450:Disease Progression; D005260:Female; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000502:physiology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology*; D015430:Weight Gain
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3
keywords: BP3KO mouse; IGFBP-3; T-cell; breast cancer; obesity