Tumor‐associated macrophages promote bladder tumor growth through PI3K/AKT signal induced by collagen

• DOI: 10.1111/cas.14078
• Publication Date: 2019-05-23T09:52:42Z
• Authors: Shi Qiu; Linghui Deng; Xinyang Liao; Ling Nie; Fang Qi; Kun Jin; Xiang Tu; Xiaonan Zheng; Jiakun Li; Liangren Liu; Zhenhua Liu; Yige Bao; Jianzhong Ai; Tianhai Lin; Lu Yang; Qiang Wei
• Keywords: 0301 basic medicine; Macrophages; Morpholines; Original Articles; Xenograft Model Antitumor Assays; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Urinary Bladder Neoplasms; Chromones; Cell Line, Tumor; Tumor Microenvironment; Animals; Humans; Collagen; Integrin alpha2beta1; Heterocyclic Compounds, 3-Ring; Proto-Oncogene Proteins c-akt; Cell Proliferation; Signal Transduction

AbstractThe tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor‐associated macrophages (TAMs) are considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2β1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2β1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.