Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer

Abstract Tetrathiomolybdate (TM) is a novel, copper-depleting compound associated with promising survival in a phase II study of patients with high-risk and triple-negative breast cancer. We sought to elucidate the mechanism of TM by exploring its effects on collagen processing and immune function i...

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Autores principales:	Ying L. Liu, Cecilie Liv Bager, Nicholas Willumsen, Divya Ramchandani, Naomi Kornhauser, Lu Ling, Marta Cobham, Eleni Andreopoulou, Tessa Cigler, Anne Moore, Dayle LaPolla, Veronica Fitzpatrick, Maureen Ward, J. David Warren, Claudia Fischbach, Vivek Mittal, Linda T. Vahdat
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/37a653a1d4054f088c420dae713f918a
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spelling	oai:doaj.org-article:37a653a1d4054f088c420dae713f918a2021-12-02T15:09:17ZTetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer10.1038/s41523-021-00313-w2374-4677https://doaj.org/article/37a653a1d4054f088c420dae713f918a2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41523-021-00313-whttps://doaj.org/toc/2374-4677Abstract Tetrathiomolybdate (TM) is a novel, copper-depleting compound associated with promising survival in a phase II study of patients with high-risk and triple-negative breast cancer. We sought to elucidate the mechanism of TM by exploring its effects on collagen processing and immune function in the tumor microenvironment (TME). Using an exploratory cohort, we identified markers of collagen processing (LOXL2, PRO-C3, C6M, and C1M) that differed between those with breast cancer versus controls. We measured these collagen biomarkers in TM-treated patients on the phase II study and detected evidence of decreased collagen cross-linking and increased degradation over formation in those without disease compared to those who experienced disease progression. Preclinical studies revealed decreased collagen deposition, lower levels of myeloid-derived suppressor cells, and higher CD4+ T-cell infiltration in TM-treated mice compared with controls. This study reveals novel mechanisms of TM targeting the TME and immune response with potential applications across cancer types.Ying L. LiuCecilie Liv BagerNicholas WillumsenDivya RamchandaniNaomi KornhauserLu LingMarta CobhamEleni AndreopoulouTessa CiglerAnne MooreDayle LaPollaVeronica FitzpatrickMaureen WardJ. David WarrenClaudia FischbachVivek MittalLinda T. VahdatNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Breast Cancer, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ying L. Liu Cecilie Liv Bager Nicholas Willumsen Divya Ramchandani Naomi Kornhauser Lu Ling Marta Cobham Eleni Andreopoulou Tessa Cigler Anne Moore Dayle LaPolla Veronica Fitzpatrick Maureen Ward J. David Warren Claudia Fischbach Vivek Mittal Linda T. Vahdat Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer
description	Abstract Tetrathiomolybdate (TM) is a novel, copper-depleting compound associated with promising survival in a phase II study of patients with high-risk and triple-negative breast cancer. We sought to elucidate the mechanism of TM by exploring its effects on collagen processing and immune function in the tumor microenvironment (TME). Using an exploratory cohort, we identified markers of collagen processing (LOXL2, PRO-C3, C6M, and C1M) that differed between those with breast cancer versus controls. We measured these collagen biomarkers in TM-treated patients on the phase II study and detected evidence of decreased collagen cross-linking and increased degradation over formation in those without disease compared to those who experienced disease progression. Preclinical studies revealed decreased collagen deposition, lower levels of myeloid-derived suppressor cells, and higher CD4+ T-cell infiltration in TM-treated mice compared with controls. This study reveals novel mechanisms of TM targeting the TME and immune response with potential applications across cancer types.
format	article
author	Ying L. Liu Cecilie Liv Bager Nicholas Willumsen Divya Ramchandani Naomi Kornhauser Lu Ling Marta Cobham Eleni Andreopoulou Tessa Cigler Anne Moore Dayle LaPolla Veronica Fitzpatrick Maureen Ward J. David Warren Claudia Fischbach Vivek Mittal Linda T. Vahdat
author_facet	Ying L. Liu Cecilie Liv Bager Nicholas Willumsen Divya Ramchandani Naomi Kornhauser Lu Ling Marta Cobham Eleni Andreopoulou Tessa Cigler Anne Moore Dayle LaPolla Veronica Fitzpatrick Maureen Ward J. David Warren Claudia Fischbach Vivek Mittal Linda T. Vahdat
author_sort	Ying L. Liu
title	Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer
title_short	Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer
title_full	Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer
title_fullStr	Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer
title_full_unstemmed	Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer
title_sort	tetrathiomolybdate (tm)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/37a653a1d4054f088c420dae713f918a
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Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer

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