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Insulin-like growth factor binding protein-3 links obesity and breast cancer progression
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 rol...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342431/ https://www.ncbi.nlm.nih.gov/pubmed/27448965 http://dx.doi.org/10.18632/oncotarget.10675 |
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author | Scully, Tiffany Firth, Sue M. Scott, Carolyn D. de Silva, Hasanthi C. Pintar, John E. Chan-Ling, Tailoi Twigg, Stephen M. Baxter, Robert C. |
author_facet | Scully, Tiffany Firth, Sue M. Scott, Carolyn D. de Silva, Hasanthi C. Pintar, John E. Chan-Ling, Tailoi Twigg, Stephen M. Baxter, Robert C. |
author_sort | Scully, Tiffany |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5342431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53424312017-03-22 Insulin-like growth factor binding protein-3 links obesity and breast cancer progression Scully, Tiffany Firth, Sue M. Scott, Carolyn D. de Silva, Hasanthi C. Pintar, John E. Chan-Ling, Tailoi Twigg, Stephen M. Baxter, Robert C. Oncotarget Research Paper 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. Impact Journals LLC 2016-07-18 /pmc/articles/PMC5342431/ /pubmed/27448965 http://dx.doi.org/10.18632/oncotarget.10675 Text en Copyright: © 2016 Scully et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Scully, Tiffany Firth, Sue M. Scott, Carolyn D. de Silva, Hasanthi C. Pintar, John E. Chan-Ling, Tailoi Twigg, Stephen M. Baxter, Robert C. Insulin-like growth factor binding protein-3 links obesity and breast cancer progression |
title | Insulin-like growth factor binding protein-3 links obesity and breast cancer progression |
title_full | Insulin-like growth factor binding protein-3 links obesity and breast cancer progression |
title_fullStr | Insulin-like growth factor binding protein-3 links obesity and breast cancer progression |
title_full_unstemmed | Insulin-like growth factor binding protein-3 links obesity and breast cancer progression |
title_short | Insulin-like growth factor binding protein-3 links obesity and breast cancer progression |
title_sort | insulin-like growth factor binding protein-3 links obesity and breast cancer progression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342431/ https://www.ncbi.nlm.nih.gov/pubmed/27448965 http://dx.doi.org/10.18632/oncotarget.10675 |
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