Inhibiting fibronectin assembly in the breast tumor microenvironment increases cell death and improves response to doxorubicin.

ABSTRACT:

Purpose

Effective therapies for solid tumors, including breast cancers, are hindered by several roadblocks that can be largely attributed to the fibrotic extracellular matrix (ECM). Fibronectin (FN) is a highly upregulated ECM component in the fibrotic tumor stroma and is associated with poor patient prognosis. This study aimed to investigate the therapeutic potential of an anti-fibrotic peptide that specifically targets FN and blocks the fibrillar assembly of FN.

Methods

To target FN, we used PEGylated Functional Upstream Domain (PEG-FUD), which binds to the 70 kDa N-terminal region of FN with high affinity, localizes to mammary tumors, and potently inhibits FN assembly in vitro and in vivo. Here, we used the 4T1 tumor model to investigate the efficacy and mechanisms of PEG

SUBMITTER: Gari MK 

PROVIDER: S-EPMC11952368 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature