T Cells Promote Metastasis by Regulating Extracellular Matrix Remodeling following Chemotherapy.

ABSTRACT: Metastasis is the main cause of cancer-related mortality. Despite intense efforts to understand the mechanisms underlying the metastatic process, treatment of metastatic cancer is still challenging. Here we describe a chemotherapy-induced, host-mediated mechanism that promotes remodeling of the extracellular matrix (ECM), ultimately facilitating cancer cell seeding and metastasis. Paclitaxel (PTX) chemotherapy enhanced rapid ECM remodeling and mechanostructural changes in the lungs of tumor-free mice, and the protein expression and activity of the ECM remodeling enzyme lysyl oxidase (LOX) increased in response to PTX. A chimeric mouse model harboring genetic LOX depletion revealed chemotherapy-induced ECM remodeling was mediated by CD8⁺ T cells expressing LOX. Consistently, adop

SUBMITTER: Haj-Shomaly J 

PROVIDER: S-EPMC7612244 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature