Enhancement of mammary tumour growth by IGFBP-3 involves impaired T cell accumulation

Scully, T; Scott, CD; Firth, SM; Sedger, LM; Pintar, JE; Twigg, SM; Baxter, RC

Enhancement of mammary tumour growth by IGFBP-3 involves impaired T cell accumulation

Scully, T Scott, CD Firth, SM Sedger, LM

Pintar, JE Twigg, SM Baxter, RC

Permalink

Publication Type:: Journal Article
Citation:: Endocrine-Related Cancer, 2018, 25 (2), pp. 111 - 122
Issue Date:: 2018-02-01

Closed Access

	Filename	Description	Size
	Scully_EtAl_ENdocrinRelatedCancer2018_Author Copy.pdf	Published Version	1.26 MB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Scully, T	en_US
dc.contributor.author	Scott, CD	en_US
dc.contributor.author	Firth, SM	en_US
dc.contributor.author	Sedger, LM https://orcid.org/0000-0003-1009-5683	en_US
dc.contributor.author	Pintar, JE	en_US
dc.contributor.author	Twigg, SM	en_US
dc.contributor.author	Baxter, RC	en_US
dc.date.available	2017-10-31	en_US
dc.date.issued	2018-02-01	en_US
dc.identifier.citation	Endocrine-Related Cancer, 2018, 25 (2), pp. 111 - 122	en_US
dc.identifier.issn	1351-0088	en_US
dc.identifier.uri	http://hdl.handle.net/10453/124510
dc.description.abstract	© 2018 Society for Endocrinology Published by Bioscientifica Ltd. Epidemiological studies show an association between obesity and poor breast cancer prognosis. We previously demonstrated that global IGFBP-3 deficiency, in IGFBP-3-null mice, resulted in a 50% reduction in mammary tumour growth over 3 weeks relative to tumours in wild-type (WT) C57BL/6 mice. This growth reduction was ameliorated by high fat feeding-induced obesity. This study aimed to examine how IGFBP-3 promotes tumour growth by influencing the immune tumour microenvironment in healthy and obese mice. Syngeneic EO771 cells, which lack detectable IGFBP-3 expression, were grown as orthotopic tumours in WT and IGFBP-3-null C57BL/6 mice placed on either a control chow or a high-fat diet (HFD), and examined by quantitative PCR and immunohistochemistry. In WT mice, increased stromal expression of IGFBP-3 was positively associated with tumour growth, supporting the hypothesis that IGFBP-3 in the microenvironment promotes tumour progression. Examining markers of immune cell subsets, gene expression of Ifng, Cd8a, Cd8b1 and TNF and CD8 measured by immunohistochemistry were elevated in tumours of IGFBP-3-null mice compared to WT, indicating an accumulation of CD8+ T cells, but this increase was absent if the IGFBP-3-null mice had been exposed to HFD. Expression of these genes was negatively associated with tumour growth. Although similar among groups overall, Nkg2d and TNFsf10 tumoural expression was associated with decreased tumour growth. Overall, the results of this study provide an immunebased mechanism by which host IGFBP-3 may promote breast tumour growth in the EO771 murine breast cancer model, and suggest that targeting IGFBP-3 might make a novel contribution to immune therapy for breast cancer.	en_US
dc.relation.ispartof	Endocrine-Related Cancer	en_US
dc.relation.isbasedon	10.1530/ERC-17-0384	en_US
dc.subject.classification	Oncology & Carcinogenesis	en_US
dc.subject.mesh	CD8-Positive T-Lymphocytes	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Mammary Neoplasms, Experimental	en_US
dc.subject.mesh	Insulin-Like Growth Factor Binding Protein 3	en_US
dc.subject.mesh	Gene Expression Profiling	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Diet, High-Fat	en_US
dc.title	Enhancement of mammary tumour growth by IGFBP-3 involves impaired T cell accumulation	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	25	en_US
utslib.for	1101 Medical Biochemistry and Metabolomics	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	25	en_US

Abstract:

© 2018 Society for Endocrinology Published by Bioscientifica Ltd. Epidemiological studies show an association between obesity and poor breast cancer prognosis. We previously demonstrated that global IGFBP-3 deficiency, in IGFBP-3-null mice, resulted in a 50% reduction in mammary tumour growth over 3 weeks relative to tumours in wild-type (WT) C57BL/6 mice. This growth reduction was ameliorated by high fat feeding-induced obesity. This study aimed to examine how IGFBP-3 promotes tumour growth by influencing the immune tumour microenvironment in healthy and obese mice. Syngeneic EO771 cells, which lack detectable IGFBP-3 expression, were grown as orthotopic tumours in WT and IGFBP-3-null C57BL/6 mice placed on either a control chow or a high-fat diet (HFD), and examined by quantitative PCR and immunohistochemistry. In WT mice, increased stromal expression of IGFBP-3 was positively associated with tumour growth, supporting the hypothesis that IGFBP-3 in the microenvironment promotes tumour progression. Examining markers of immune cell subsets, gene expression of Ifng, Cd8a, Cd8b1 and TNF and CD8 measured by immunohistochemistry were elevated in tumours of IGFBP-3-null mice compared to WT, indicating an accumulation of CD8+ T cells, but this increase was absent if the IGFBP-3-null mice had been exposed to HFD. Expression of these genes was negatively associated with tumour growth. Although similar among groups overall, Nkg2d and TNFsf10 tumoural expression was associated with decreased tumour growth. Overall, the results of this study provide an immunebased mechanism by which host IGFBP-3 may promote breast tumour growth in the EO771 murine breast cancer model, and suggest that targeting IGFBP-3 might make a novel contribution to immune therapy for breast cancer.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/124510