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Association of breast carcinoma growth with a non-canonical axis of IFNγ/IDO1/TSP1

Lopes-Bastos, Bruno, Jin, Liang, Ruge, Fiona, Owen, Sioned, Sanders, Andrew J. ORCID:, Cogle, Christopher, Chester, John D. ORCID:, Jiang, Wen Guo ORCID: and Cai, Jun 2017. Association of breast carcinoma growth with a non-canonical axis of IFNγ/IDO1/TSP1. Oncotarget 10.18632/oncotarget.18781

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Reciprocal interactions between cancers and the surrounding microenvironment have an important role in tumour evolution. In this study, our data suggested that through thrombospondin 1 (TSP1), tumour-associated microvessel provides a dormant niche to sustain inactive status of breast invasive ductal carcinoma (IDC) cells. TSP1 levels in the tumour stroma were negatively correlated with vascular indoleamine 2,3-dioxygenase 1 (IDO1) in IDC tissues. IDO1 is an intracellular enzyme initiating the first and rate-limited step of tryptophan breakdown. Lower stromal TSP1 levels and positive tumour vascular IDO1 staining seems to associate with poor survive of patients with IDC. IDC cells induced a significantly increase in IDO1 expression in endothelial cells (ECs). IFNγ exerts a similar effect on ECs. We hypothesized a tryptophan starvation theory that since tryptophan is essential for the synthesis of TSP1, IDO1 induce a decrease in tryptophan availability and a reduction in TSP1 synthesis in ECs, leading to overcoming the dormancy state of IDC cells and exacerbating conditions such as tumour invasion and metastasis. These findings identify a non-canonical role of IFNγ/IDO1/TSP1 axis in microvascular niche-dominated dormancy of breast invasive ductal carcinoma with a solid foundation for further investigation of therapeutic and prognostic relevance.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Uncontrolled Keywords: IFNγ, IDO1, TSP1, endothelial cells, breast invasive ductal carcinoma
Publisher: Impact Journals LLC
ISSN: 1949-2553
Funders: Cancer Research Wales, Life Sciences Research Network Wales
Date of First Compliant Deposit: 3 July 2017
Date of Acceptance: 29 May 2017
Last Modified: 11 Oct 2023 17:13

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