Department of Urology, Institute of Urology and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, China.
Center of Biomedical Big Data, West China Hospital, Sichuan University, Chengdu, China.
Cancer Sci. 2019 Jul;110(7):2110-2118. doi: 10.1111/cas.14078. Epub 2019 Jun 19.
The 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.
肿瘤微环境与多种肿瘤进展相关，包括癌症转移、免疫抑制和肿瘤持续生长。肿瘤相关巨噬细胞（TAMs）被认为是肿瘤微环境中不可或缺的组成部分，参与肿瘤微环境重塑的进展，并产生各种化合物来调节肿瘤活动。本研究旨在观察膀胱癌发展过程中肿瘤组织中富集的 TAMs，这些 TAMs 明显促进了膀胱癌细胞的增殖，并促进了体内肿瘤的生长。我们发现 TAMs 通过分泌 I 型胶原来调节肿瘤的持续生长，该胶原可激活促进生存的整合素 α2β1/PI3K/AKT 信号通路。此外，传统化疗药物联合整合素 α2β1 抑制剂显示出强烈的抗癌作用，为临床膀胱癌治疗提供了一种创新方法。
