Journal Article

DDR1 promotes breast tumor growth by suppressing antitumor immunity

Zhang, Weiwei, Sun, Tianhao, Zhong, Xing

2019

Overview

Breast cancer is the second leading cause of cancer-associated mortality among women worldwide. Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and is defined by its aggressive nature and limited treatment options. Therefore, there is an urgent need to develop effective therapies for TNBC in order to improve breast cancer outcomes, as targeted therapies have done in other subtypes of breast cancer. Discoidin domain receptor tyrosine kinase 1 (DDR1) is activated by collagens, which are important components of the tumor stroma; therefore, DDR1 may serve a critical role in the communication between tumor cells and the tumor microenvironment. The aim of the present study was to determine how tumor DDR1 regulated tumor growth by affecting tumor infiltrated T cells. First, the DDR1 expression levels from a cohort of patients with breast cancer were analyzed. The results revealed that there were higher levels of DDR1 expression in tumor tissues compared with adjacent normal tissues. Overexpression of DDR1 in 4T1 cells promoted tumor growth in vivo, while knockout of DDR1 in EMT6 cells decreased tumor growth in vivo. In addition, it was revealed that DDR1 regulated tumor growth by modulating tumor infiltrating T cells, CD4+ and CD8+. Furthermore, inhibition of DDR1 by neutralizing antibodies decreased breast cancer growth in vivo. To the best of our knowledge, the results of the present study demonstrated for the first time that DDR1 expressed on the tumor cells promoted breast tumor growth by suppressing antitumor immunity. The present findings indicated that DDR1 may not only have a critical role in the progression of breast cancer, but may also serve as a potential therapeutic target for breast cancer, particularly TNBC.

• Publisher: D.A. Spandidos,Spandidos Publications,Spandidos Publications UK Ltd
• Subject: Adult / Analysis / Animal genetic engineering / Animals / Antibodies / Breast cancer / CD4+ T cell / CD8+ T cells / Cell Line, Tumor / Cell Movement - genetics / Cell Proliferation - genetics / Cloning / CRISPR / Cytotoxicity / Development and progression / Discoidin Domain Receptor 1 - antagonists & inhibitors / Discoidin Domain Receptor 1 - genetics / Discoidin Domain Receptor 1 - immunology / discoidin domain receptor tyrosine kinase 1 / EDTA / Ethylenediaminetetraacetic acid / extracellular domain / Female / Gene expression / Gene Expression Regulation, Neoplastic - genetics / Growth / Health aspects / Humans / Immunity, Innate - genetics / Immunotherapy / Kinases / Laboratory animals / Lung cancer / Lymphocytes / Mice / Middle Aged / Mutation / Phenols (Class of compounds) / Plasmids / Scientific equipment and supplies industry / Scientific equipment industry / Studies / T cells / T-Lymphocytes - immunology / T-Lymphocytes - pathology / Transfection / Triple Negative Breast Neoplasms - genetics / Triple Negative Breast Neoplasms - immunology / Triple Negative Breast Neoplasms - pathology / tumor growth / Tumor Microenvironment - genetics / Tumor Microenvironment - immunology / Tumors / Tyrosine / Vaccines / Viral antibodies