The role of tumor-derived exosomes in tumor angiogenesis and tumor progression

Abstract

Exosomes, belonging to the group of extracellular bodies, are released by healthy as well as cancerous cells and serve as a communication pathway. Tumor-derived exosomes (TEX) possess the capacity to reprogram the function of normal cells owing to their genetic and molecular cargo. Such exosomes target endothelial cells (among others) in the tumor microenvironment to promote angiogenesis. Blood supply is essential in solid tumor growth and metastasis. The potential of pro-angiogenic changes is enhanced by an increased amount of circulating tumor-derived exosomes in the body fluids of cancer patients. A vascular network is important, since the proliferation, as well as the metastatic spread of cancer cells depends on an adequate supply of oxygen and nutrients, and the removal of waste products. New blood vessels and lymphatic vessels are formed through processes called angiogenesis and lymphangiogenesis, respectively. Angiogenesis is regulated by both activator and inhibitor molecules. Thousands of patients have received anti-angiogenic therapy to date. Despite their theoretical efficacy, anti-angiogenic treatments have not proved beneficial in terms of long-term survival. Tumor-derived exosomes carrying pro-angiogenic factors might be a target for new anti-cancer therapy.

The updated role of exosomal proteins in the diagnosis, prognosis, and treatment of cancer

“…Tumor-derived (TD) exosomes are released by tumor cells and carry substances that can reflect the features of the parental tumor cell 4 . Therefore, exosomes can be applied as tumor diagnostic markers.…”

Targeting hypoxia signaling pathways in angiogenesis

“…Hypoxic condition within the tumor environment enhances the release of tumor-derived exosomes (TEX) and act as a potent trigger for the communication between cancer and ECs. After the uptake by ECs, TEX transfers molecular information, which promotes their adhesion, proliferation, migration, tube formation, and as a result pathological angiogenesis ( Gluszko et al, 2019 ). In breast cancer, MSC-derived exosomes induce a significant and dose-dependent decrease in the expression and secretion of VEGF through the modulation of the mTOR/HIF-1α signaling axis, suggesting an important potential therapeutic target for this type of tumor ( Pakravan et al, 2017 ).…”

Roles of Extracellular Vesicles in Cancer Metastasis

“…Upregulation of Heparanase in tumor cells, such as myeloma and breast malignancies, has also been linked to increased exosome production and exosomal packing of Syndecan-1, VEGF, and hepatocyte growth factor, resulting in enhanced endothelial invasion through the ECM [38]. Exo produced from skin cancer can also enhance angiogenesis by transferring the EGFR [39] and miR-9 to ECs [26]. Furthermore, melanoma-derived Exo have been found to condition sentinel lymph nodes prior to the installation of melanoma cells and subsequent metastasis by upregulating Collagen 18 and Laminin 5, as well as producing angiogenic growth factors [26].…”