Insulin-like growth factor binding protein-3 links obesity and breast cancer progression
| Autor: | Robert C. Baxter, John E. Pintar, Sue M. Firth, Tiffany Scully, Tailoi Chan-Ling, Carolyn D. Scott, Stephen M. Twigg, Hasanthi C. de Silva |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
obesity medicine.medical_specialty Stromal cell Adipose tissue Apoptosis Breast Neoplasms Diet High-Fat Weight Gain medicine.disease_cause Mice 03 medical and health sciences chemistry.chemical_compound breast cancer Lymphocytes Tumor-Infiltrating 0302 clinical medicine Breast cancer T-cell Cell Movement Internal medicine Adipocyte Animals Medicine Mice Knockout Mammary tumor business.industry Cancer IGFBP-3 medicine.disease Obesity BP3KO mouse Mice Inbred C57BL Insulin-Like Growth Factor Binding Protein 3 030104 developmental biology Endocrinology Adipose Tissue Oncology chemistry 030220 oncology & carcinogenesis Immunology Disease Progression Female business Carcinogenesis Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.10675 |
| Popis: | // Tiffany Scully 1 , Sue M. Firth 1 , Carolyn D. Scott 1 , Hasanthi C. de Silva 1 , John E. Pintar 2 , Tailoi Chan-Ling 3 , Stephen M. Twigg 4 , Robert C. Baxter 1 1 Hormones and Cancer Laboratories, Kolling Institute, University of Sydney, Royal North Shore Hospital, Sydney, New South Wales 2065, Australia 2 Department of Neuroscience and Cell Biology, Rutgers University, Robert Wood Johnson Medical School, New Brunswick, NJ 08854, USA 3 Department of Anatomy, Bosch Institute, University of Sydney, Sydney, New South Wales 2006, Australia 4 Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, New South Wales 2006, Australia Correspondence to: Robert C. Baxter, email: robert.baxter@sydney.edu.au Keywords: IGFBP-3, obesity, breast cancer, BP3KO mouse, T-cell Received: January 21, 2016 Accepted: June 16, 2016 Published: July 18, 2016 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 mm 3 , 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. |
| Databáze: | OpenAIRE |
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