scholarly journals Landscape of cancer-associated fibroblasts identifies the secreted biglycan as a protumor and immunosuppressive factor in triple-negative breast cancer

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Shaoquan Zheng ◽  
Yutian Zou ◽  
Yuhui Tang ◽  
Anli Yang ◽  
Jie-Ying Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Associated Fibroblasts ◽  
Immunosuppressive Factor

scholarly journals Prognostic significance of PD-L1-positive cancer-associated fibroblasts in patients with triple-negative breast cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Katsuhiro Yoshikawa ◽  
Mitsuaki Ishida ◽  
Hirotsugu Yanai ◽  
Koji Tsuta ◽  
Mitsugu Sekimoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Tissue Microarrays ◽  
Tumour Microenvironment ◽  
Clinicopathological Parameters ◽  
Cancer Associated Fibroblasts ◽  
Clinicopathological Significance

Abstract Background Cancer-associated fibroblasts (CAFs) are some of the most abundant components of the tumour microenvironment. A recent study suggested that in some cancers, CAFs express programmed death ligand 1 (PD-L1), which can act as a prognostic marker. The aim of this study was to investigate the clinicopathological significance of CAF PD-L1 expression in patients with triple-negative breast cancer (TNBC) and to identify the most suitable primary antibody for immunostaining for CAF PD-L1. Methods Immunohistochemical staining (primary antibodies of 73–10, SP142, and E1L3N) and tissue microarrays were used to analyse the expression profiles of PD-L1 in CAF in 61 patients with TNBC who underwent surgery. Overall survival (OS) was compared based on CAF PD-L1 expression, and the risk factors for OS were analysed. The relationship between clinicopathological parameters and survival was also examined. Results Thirty-four (55.7%) patients were positive for CAF PD-L1 (73–10) expression. Compared with CAF PD-L1 negativity, there was a significant correlation between CAF PD-L1 positivity and better OS (p = 0.029). CAF PD-L1 expression, evaluated using SP-142 or E1L3N, did not correlate with OS. CAF PD-L1-positivity (73–10) correlated significantly with better prognosis in multivariate analyses (hazard ratio: 0.198; 95% confidence interval: 0.044–0.891; p = 0.035). Conclusions CAF PD-L1 expression is a novel marker for a better prognosis of patients with TNBC, and the 73–10 assay may be suitable for immunostaining CAF PD-L1.

scholarly journals Targeting the cancer-associated fibroblasts as a treatment in triple-negative breast cancer

Oncotarget ◽  
2016 ◽  
Vol 7 (50) ◽  
pp. 82889-82901 ◽  
Author(s):  
Ken Takai ◽  
Annie Le ◽  
Valerie M. Weaver ◽  
Zena Werb
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Associated Fibroblasts

scholarly journals Cancer-Associated Fibroblasts Autophagy Enhances Progression of Triple-Negative Breast Cancer Cells

2017 ◽  
Vol 23 ◽  
pp. 3904-3912 ◽  
Author(s):  
Mengchuan Wang ◽  
Jian Zhang ◽  
Yizhe Huang ◽  
Shufeng Ji ◽  
Guoli Shao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Cancer Associated Fibroblasts

scholarly journals SPARC in cancer-associated fibroblasts is an independent poor prognostic factor in non-metastatic triple-negative breast cancer and exhibits pro-tumor activity

2021 ◽  
Author(s):  
Lindsay B Alcaraz ◽  
Aude Mallavialle ◽  
Caroline Mollevi ◽  
Florence Boissiere Michot ◽  
Hanane Mansouri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Prognostic Factor ◽  
Triple Negative Breast Cancer ◽  
Stromal Cell ◽  
Triple Negative ◽  
Cancer Associated Fibroblasts ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Sparc Expression

Purpose: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and lacks specific targeted therapeutics. The current mechanistic evidence from cell-based studies suggests that the matricellular protein SPARC has a tumor-promoting role in TNBC; however, data on the clinical relevance of SPARC expression/secretion by tumor and stromal cells in TNBC are limited. Experimental Design: This study analyzed the prognostic value of tumor and stromal cell SPARC expression in a large series of 148 patients with non-metastatic TNBC and long follow-up (median: 5.4 years). Fibrosis, tumor-associated macrophage (TAM) infiltration, tumor-infiltrating lymphocyte (TIL) density, PD-L1 and PD-1 expression were assessed. Tumor and stromal cell SPARC expression was studied by immunofluorescence, western blotting, and meta-analysis of published single-cell mRNA sequencing data. The biological role of fibroblast-secreted SPARC was analyzed using cell adhesion, wound healing, Transwell-based motility and invasion, and tumor spheroid assays. Results: SPARC expression was detected in cancer cells (42.4%), cancer-associated fibroblasts (CAFs) (88.1%), TAMs (77.1%), endothelial cells (75.2%), and TILs (9.8%). Recurrence-free survival was significantly lower in patients with SPARC-expressing CAFs. SPARC expression in CAFs was an independent prognostic factor in multivariate analysis. Tumor and stromal cell SPARC expression was observed in TNBC cytosols, patient-derived xenografts, and cell lines. SPARC was expressed by different CAF subsets, including myofibroblasts and inflammatory CAFs. Fibroblast-secreted SPARC inhibited TNBC cell adhesion and stimulated their migration and invasion. Conclusions: SPARC expression in CAFs is an independent predictor of recurrence-free survival in TNBC. Patients with SPARC-expressing CAFs could be eligible for anti-SPARC-targeted therapy.

Sign in / Sign up

Export Citation Format

Share Document