Abstract
Angiogenesis is the process through which new blood vessels are formed from pre-existing ones. Exosomes are involved in angiogenesis in cancer progression by transporting numerous pro-angiogenic biomolecules like vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), and microRNAs. Exosomes promote angiogenesis by suppressing expression of factor-inhibiting hypoxia-inducible factor 1 (HIF-1). Uptake of tumor-derived exosomes (TEX) by normal endothelial cells activates angiogenic signaling pathways in endothelial cells and stimulates new vessel formation. TEX-driven cross-talk of mesenchymal stem cells (MSCs) with immune cells blocks their anti-tumor activity. Effective inhibition of tumor angiogenesis may arrest tumor progression. Bevacizumab, a VEGF-specific antibody, was the first antiangiogenic agent to enter the clinic. The most important clinical problem associated with cancer therapy using VEGF- or VEFGR-targeting agents is drug resistance. Combined strategies based on angiogenesis inhibitors and immunotherapy effectively enhances therapies in various cancers, but effective treatment requires further research.
Highlights
Angiogenesis and inflammation are processes that play important roles in the development of cancer, from the initiation of carcinogenesis, the carcinoma in situ stage, to the advanced stages of cancer [1]
Angiogenesis is controlled by various angiogenic and anti-angiogenic factors, which are carried by exosomes
Combined strategies based on angiogenesis inhibitors and immunotherapy effectively enhances the benefits of therapies in cancers [211]
Summary
Angiogenesis and inflammation are processes that play important roles in the development of cancer, from the initiation of carcinogenesis, the carcinoma in situ stage, to the advanced stages of cancer [1]. Excessive abnormal angiogenesis has a central role in tumor progression. It is induced by an imbalance between pro- and anti-angiogenic factors, dominated by tissue hypoxia-triggered overproduction of vascular endothelial growth factor (VEGF) [2]. Tumor cells utilize different strategies to communicate with neighboring tissues for facilitating tumor progression; one of these strategies is a release of exosomes [4,5]. There is evidence that noncoding RNAs, especially long non-coding RNAs (lncRNAs) and microRNAs, play important roles in the regulation of angiogenesis [10]. It has been shown that tumor vasculogenesis and progression after anti-angiogenic therapies (AATs) and anti-autophagic therapies are due to cross-talk between endothelial and tumor cells via VEGF-enriched exosomes [11]. This review will consider exosomes in the context of tumor angiogenesis and the limited efficacy of current anti-angiogenic approaches
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