Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer

Author:

Ma Bin12,Li Fangfang2,Ma Binlin3

Affiliation:

1. Department of Thyriod and Breast Surgery, West China School of Public Health, West China Fourth Hospital, Sichuan University , Chengdu 610041 , China

2. Department of Breast and Thyroid Surgery, The Affiliated Cancer Hospital of Xinjiang Medical University , Urumqi 830011, Xinjiang , China

3. Department of Breast and Thyroid Surgery, The Affiliated Cancer Hospital of Xinjiang Medical University , No. 789 Suzhou East Street , Urumqi 830011, Xinjiang , China

Abstract

Abstract We investigated the effects of collagen type I alpha 1 (COL1A1) on tumor-associated fibroblast activation and matrix remodeling in the tumor microenvironment of breast cancer. Cells were divided into the blank control, negative control, and siRNA-COL1A1 groups, or HKF control, HKF + exosomes (EXO), HKF + siRNA negative control-EXO, and HKF + siRNA-COL1A1-EXO co-culture groups. Western blot and quantitative real-time PCR detected gene expressions. COL Ⅰ, COL Ⅲ, and TGF-β1 were detected by enzyme-linked immunosorbent assay. We found that compared with blank and negative control groups, COL1A1 expression and the secretion of exosomes by breast cancer cells were inhibited in the siRNA-COL1A1 group. Compared with the HKF control group, the COL Ⅰ, COL Ⅲ, TGF-β1, α-SMA, and fibroblast activation protein (FAP) were increased, while the E-cadherin and CAV-1 were decreased in the HKF + EXO, HKF + siRNA negative control-EXO, and HKF + siRNA-COL1A1-EXO co-culture groups. Compared with HKF + EXO and HKF + siRNA negative control-EXO co-culture groups, the COL Ⅰ, COL Ⅲ, TGF-β1, α-SMA, and FAP were decreased, and the E-cadherin and CAV-1 were increased in the HKF + siRNA-COL1A1-EXO co-culture group. Collectively, COL1A1 down-regulation may inhibit exosome secretion possibly via inhibiting COL Ⅰ and upregulating CAV-1, thereby inhibiting tumor-associated fibroblast activation and matrix remodeling in the tumor microenvironment.

Publisher

Walter de Gruyter GmbH

Subject

General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience

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