Recombinant Human Decorin Normalizes the Active Features of Breast Cancer-Associated Fibroblasts.

Area of Science:

• Oncology
• Cell Biology
• Biochemistry

Background:

• Cancer-associated fibroblasts (CAFs) are key drivers of tumor progression, resistance, recurrence, and metastasis.
• CAFs significantly contribute to the tumor microenvironment's complex signaling network.

Purpose of the Study:

• To investigate the potential of decorin (DCN), an oncogene suppressor, in normalizing active breast CAFs.
• To evaluate rhDCN's effects on CAF biomarkers and their pro-tumorigenic functions.

Main Methods:

• Investigated rhDCN's modulation of protein expression in signaling pathways (STAT3/NF-κB, ERK).
• Assessed rhDCN's impact on CAF biomarkers (α-SMA, IL-6, SDF-1, FAP-α) in 2D and 3D cultures.
• Evaluated rhDCN's effects on CAF-mediated promotion of epithelial-to-mesenchymal transition (EMT) and cancer stem cells in vitro and in vivo.

Main Results:

• rhDCN repressed key CAF biomarkers (α-SMA, IL-6, SDF-1) via STAT3/AUF-1 pathway inhibition.
• rhDCN downregulated FAP-α and suppressed CAF proliferation and invasion by modulating p16, p21, MMP-2, and MMP-9.
• rhDCN effectively suppressed CAF-driven EMT and cancer stem cell generation without cytotoxicity, with persistent effects.

Conclusions:

• rhDCN effectively normalizes active CAFs, reducing their pro-tumorigenic and metastasis-promoting functions.
• rhDCN demonstrates potential as an anti-breast cancer therapeutic cytokine by targeting CAF-mediated non-cell-autonomous effects.