Revisiting tumor angiogenesis: vessel co-option, vessel remodeling, and cancer cell-derived vasculature formation

Abstract

Tumor growth and metastasis depend on the establishment of tumor vasculature to provide oxygen, nutrients, and other essential factors. The well-known vascular endothelial growth factor (VEGF) signaling is crucial for sprouting angiogenesis as well as recruitment of circulating progenitor endothelial cells to tumor vasculature, which has become therapeutic targets in clinical practice. However, the survival benefits gained from targeting VEGF signaling have been very limited, with the inevitable development of treatment resistance. In this article, we discuss the most recent findings and understanding on how solid tumors evade VEGF-targeted therapy, with a special focus on vessel co-option, vessel remodeling, and tumor cell-derived vasculature establishment. Vessel co-option may occur in tumors independently of sprouting angiogenesis, and sprouting angiogenesis is not always required for tumor growth. The differences between vessel-like structure and tubule-like structure formed by tumor cells are also introduced. The exploration of the underlying mechanisms of these alternative angiogenic approaches would not only widen our knowledge of tumor angiogenesis but also provide novel therapeutic targets for better controlling cancer growth and metastasis.

The significance of TRIP11 and T3 signaling pathway in renal cancer progression and survival of patients.

“…GLUT1 is a glucose transporter commonly upregulated in cancers, which facilitates enhanced glucose uptake and the pro-proliferative metabolic switch in tumour cells [26]. VEGFA is an important growth factor enabling activation of angiogenesis in solid tumours [27][28][29][30][31][32]. Remarkably, all of these three genes are commonly regulated by thyroid hormone signalling and hypoxia [12-14, 23, 24].…”

Angiotropism in recurrent cutaneous squamous cell carcinoma: Implications for regional tumor recurrence and extravascular migratory spread

“…Induction of platelet‐derived growth factor receptor, beta polypeptide expression in a subpopulation of melanoma cells exhibiting angiotropism may one of the mechanisms attributing to resistance to B‐Raf Proto‐Oncogene‐inhibitor therapy . In highly aggressive tumors, blood supply is maintained not only through angiogenesis, but also through incorporation of normal blood vessels from the surrounding uninvolved tissue into the growing tumor, a phenomenon called “vessel co‐option.” These co‐opted blood vessels tend to have wider lumina and are supported by pericytes as well as tumor cells in pericytic location. This phenomenon has been shown to be a mechanism of resistance to anti‐angiogenic therapy in metastatic colorectal carcinoma, metastatic lung carcinoma, hepatocellular carcinoma, and glioblastoma, among others.…”

Targeting Angiogenesis in Cancer Treatments: Where do we Stand?

“…Consequently, the impact of current angiogenesis suppressing therapies on overall patient survival has been somewhat disappointing primarily due to development of drug resistance (92)(93)(94)(95)(96)(97)(98). One of the potential reasons for those observations might be related to the discovery of numerous compensatory vascular mechanisms existing in tumors.…”