Characterization of Chemotherapy-treated PyMT Liver Matrisome

ABSTRACT: Metastasis accounts for 90% of cancer-related deaths, yet the mechanisms by which cancer cells colonize secondary organs remain poorly understood. For breast cancer patients, metastasis to the liver is associated with poor prognosis and a median survival of 6 months. Standard of care is chemotherapy, but recurrence occurs in 30% of patients. Systemic chemotherapy has been shown to induce hepatotoxicity and fibrosis, but how chemotherapy impacts the composition of the liver extracellular matrix (ECM) remains unknown. Individual ECM proteins drive tumor cell proliferation and invasion, features that are essential for metastatic outgrowth in the liver. Here, we characterize the liver ECM of tumor-bearing mice treated with and without chemotherapy using the MMTV-PyMT transgenic model of breast cancer. We identify distinct drug-specific changes induced by commonly used cytotoxic chemotherapies. We identify Collagen V as an ECM protein that is more abundant in livers isolated from paclitaxel-treated mice and identify mechanisms of Collagen V driven invasion via ECM organization and signaling through α1β1 integrins.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

DISEASE(S): Breast Cancer

SUBMITTER: Justinne Guarin  

LAB HEAD: Madeleine J Oudin

PROVIDER: PXD036736 | Pride | 2022-10-05

REPOSITORIES: Pride