Silencing of COL3A1 represses proliferation, migration, invasion, and immune escape of triple negative breast cancer cells via down‐regulating PD‐L1 expression

Abstract

This study is designed to illuminate the specific role and underlying mechanism of collagen type III alpha 1 chain (COL3A1) in triple negative breast cancer (TNBC).Quantitative real-time polymerase chain reaction was applied to examine mRNA expression of COL3A1. Western blot analysis was employed to determine protein levels of COL3A1, programmed death ligand 1 (PD-L1), Bcl-2, and cleaved caspase-3. Immunohistochemistry staining was utilized for assessing protein expression of Ki67 and COL3A1 in tissues. The proliferous capacity of cells was assessed through CCK-8 assay and 5-Ethynyl-2′-deoxyuridine assay. Cell apoptosis and the percentage of CD8 + T cells were measured using flow cytometry. Migration and invasion of TNBC cells were examined via transwell assay. Lactate dehydrogenase (LDH) release was measured via a LDH assay kit. For establishing a xenograft tumor model, MDA-MB-231 cells were injected into the flank of mice through subcutaneous injection. COL3A1 expression was raised in TNBC tissues and cells, and it was inversely associated with overall survival data of TNBC patients. COL3A1 downregulation repressed proliferation, invasion, migration, and immune escape of TNBC cells along with tumor growth of xenograft mice. In TNBC cells and tumor tissues of mice, protein expression of PD-L1 was reduced by COL3A1 knockdown. COL3A1 knockdown-mediated inhibitory effects on cell proliferation, migration, invasion, and immune escape were reversed by PD-L1 upregulation in vitro. Silencing of COL3A1 exerted an antitumor role in TNBC, implying its potential as a therapeutic target for TNBC.

COL3A1 Overexpression Associates with Poor Prognosis and Cisplatin Resistance in Lung Cancer

“…In addition, COL3A1 was overexpressed in TNBC tissues and cells and was linked to a lower OS rate. 27 Further, COL3A1 silencing caused significant inhibitions in in vitro cell proliferation, invasion, migration, and immune escape and in vivo tumor growth in xenograft mice, suggesting that COL3A1 has an oncogenic role in TNBC. COL3A1 was overexpressed in breast cancer tissues compared with controls, and its expression was further upregulated by radiation, 28 indicating that COL3A1 might be implicated in regulating the radiation resistance of breast cancer.…”

Tumor-restrictive type III collagen in the breast cancer microenvironment: prognostic and therapeutic implications

“…To date, the literature related to the role of Col3 in the breast cancer microenvironment remains conflicted with both reports on its associations with both tumor-permissive and tumor-restrictive behaviors 28,37,38,47,48,[83][84][85] . With respect to the association of Col3 with malignant behavior and prognosis in breast cancer patients, we hypothesized that In prior studies that examined associations between fibrillar collagen expression and human breast cancer behavior in vivo, Col3 expression has been associated with both more and less aggressive tumor behavior.…”

Unveiling Collagen’s Role in Breast Cancer: Insights into Expression Patterns, Functions and Clinical Implications

“… 87 Silencing of COL3A1 can inhibit the proliferation, invasion, migration, and immune escape of breast cancer cells. 88 …”

“… 90 Knocking down COL3A1 leads to reduced protein expression of PD-L1, suggesting a reverse correlation between PD-L1 upregulation and the inhibitory effects mediated by COL3A1 knockdown. 88 …”