Elevated MMP1 Expression in Carcinoma-Associated Fibroblasts of Breast Cancer Contributes to Tumor Progression and Unfavorable Prognosis.

OBJECTIVE: Previous studies have shown that cancer-associated fibroblasts (CAFs) may play a role in tumor growth and development through paracrine action. Several studies reported upregulated matrix metallopeptidase 1 (MMP1) expression in various cancers. The aim is to investigate the role of elevated MMP1 expression in CAFs of breast cancer.

METHODS: A total of 203 cases were used for immunohistochemical analysis based on multiple clinical parameters. Tissues for primary cultures of CAFs were collected from 10 breast cancer patients who underwent complete surgical resection of their tumors. MMP1 expression in primary CAFs was detected using reverse transcription-quantitative PCR and western blotting. MMP1-overexpressing CAFs were established via lentiviral transfection, followed by cell functional assays and animal xenograft experiments.

RESULTS: MMP1 expression in CAFs of breast cancer was significantly associated with T stage, triple-negative breast cancer status, neoadjuvant chemotherapy status and Ki67 expression. Additionally, MMP1 expression was closely correlated with unfavorable prognosis based on overall survival and disease-free survival analyses. Elevated MMP1 expression in CAFs was verified to promote cell adhesion, invasion, proliferation abilities and attenuate chemosensitivity to Taxotere treatment.

CONCLUSION: The results indicated that MMP1 expression in CAFs may participate in the malignant phenotype and unfavorable prognosis of breast cancer.