The role of microenvironment in tumor angiogenesis
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(2020) 39:204
REVIEW
Open Access
The role of microenvironment in tumor angiogenesis Xianjie Jiang1,2, Jie Wang2, Xiangying Deng2, Fang Xiong3, Shanshan Zhang3, Zhaojian Gong4, Xiayu Li5, Ke Cao5, Hao Deng5, Yi He1, Qianjin Liao1, Bo Xiang1,2, Ming Zhou1,2, Can Guo2, Zhaoyang Zeng1,2, Guiyuan Li1,2, Xiaoling Li1,2* and Wei Xiong1,2*
Abstract Tumor angiogenesis is necessary for the continued survival and development of tumor cells, and plays an important role in their growth, invasion, and metastasis. The tumor microenvironment—composed of tumor cells, surrounding cells, and secreted cytokines—provides a conducive environment for the growth and survival of tumors. Different components of the tumor microenvironment can regulate tumor development. In this review, we have discussed the regulatory role of the microenvironment in tumor angiogenesis. High expression of angiogenic factors and inflammatory cytokines in the tumor microenvironment, as well as hypoxia, are presumed to be the reasons for poor therapeutic efficacy of current anti-angiogenic drugs. A combination of anti-angiogenic drugs and antitumor inflammatory drugs or hypoxia inhibitors might improve the therapeutic outcome. Keywords: Tumor angiogenesis, Tumor microenvironment, Angiogenic factor, Inflammatory factor, Hypoxia inhibitor
Background Nutrients, oxygen, metabolites, chemical mediators, and metabolic waste can be transported through blood vessels between cells to maintain homeostasis of the immune system, body temperature, and pH [1]. Blood vessels play an important role in embryonic development, body growth, and wound healing. Neovascularization is an important process for the growth and metastasis of tumors, and is used to transport nutrients and remove metabolic waste from tumor cells. Several studies have showed that neovascularization is essential for tumor growth beyond 1–2 mm in diameter [2, 3]. During vasculogenesis, endothelial progenitor cells derived from hemangioblasts are recruited and differentiate into mature vascular endothelial cells when stimulated * Correspondence: [email protected]; [email protected] 1 NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China Full list of author information is available at the end of the article
by the local environment and eventually form blood vessels [4]. The physiological process through which new blood vessels are formed from pre-existing blood vessels is called angiogenesis. The angiogenic process is divided into the following steps: pro-angiogenic factors are initially secreted into the extracellular fluid to activate endothelial cells. These endothelial cells migrate along the concentration gradient of pro-angiogenic factors and attach to the blood vessels to form a functional vascular network [5]. Tumor tissues have high angiogenic capacity. Blood vessels in tumor tissues are primarily composed of endothelial cells. Blood capillaries in normal tissue undergo expansion
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