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

   

Authors:	Liu, Y. L.; Bager, C. L.; Willumsen, N.; Ramchandani, D.; Kornhauser, N.; Ling, L.; Cobham, M.; Andreopoulou, E.; Cigler, T.; Moore, A.; LaPolla, D.; Fitzpatrick, V.; Ward, M.; Warren, J. D.; Fischbach, C.; Mittal, V.; Vahdat, L. T.
Article Title:	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 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. © 2021, The Author(s).
Journal Title:	npj Breast Cancer
Volume:	7
ISSN:	2374-4677
Publisher:	Nature Publishing Group
Date Published:	2021-08-23
Start Page:	108
Language:	English
DOI:	10.1038/s41523-021-00313-w
PROVIDER:	scopus
PUBMED:	34426581
PMCID:	PMC8382701
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85113295291&doi=10.1038%2fs41523-021-00313-w&partnerID=40&md5=68def79de2c22fce7766d0af10db770a
Notes:	Article -- Export Date: 1 September 2021 -- Source: Scopus

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