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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number108
Journalnpj Breast Cancer
Volume7
Issue number1
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer'. Together they form a unique fingerprint.

Cite this