Role of Angiopoietins in Development of Cancer and Neoplasia Associated with Viral Infection

Abstract

Angiopoietin/tyrosine protein kinase receptor Tie-2 signaling in endothelial cells plays an essential role in angiogenesis and wound healing. Angiopoietin-1 (Ang-1) is crucial for blood vessel maturation while angiopoietin-2 (Ang-2), in collaboration with vascular endothelial growth factor (VEGF), initiates angiogenesis by destabilizing existing blood vessels. In healthy people, the Ang-1 level is sustained while Ang-2 expression is restricted. In cancer patients, Ang-2 level is elevated, which correlates with poor prognosis. Ang-2 not only drives tumor angiogenesis but also attracts infiltration of myeloid cells. The latter rapidly differentiate into tumor stromal cells that foster tumor angiogenesis and progression, and weaken the host’s anti-tumor immunity. Moreover, through integrin signaling, Ang-2 induces expression of matrix metallopeptidases (MMPs) to promote tumor cell invasion and metastasis. Many oncogenic viruses induce expression of Ang-2 to promote development of neoplasia associated with viral infection. Multiple Ang-2 inhibitors exhibit remarkable anti-tumor activities, further highlighting the importance of Ang-2 in cancer development.

COVID-19-associated vasculitis and vasculopathy

“…Angiopoietin-1 tyrosine protein kinase receptor related Tie-2 signaling in endothelial cells plays a pivotal role in wound healing, vascular integrity and angiogenesis [25]. Individually, angiopoietin (ANG)-1 is essential for blood vessel growth and maturation, and ANG-2 acts in combination with vascular endothelial cell growth factor (VEGF) to initiate angiogenesis.…”

“…Individually, angiopoietin (ANG)-1 is essential for blood vessel growth and maturation, and ANG-2 acts in combination with vascular endothelial cell growth factor (VEGF) to initiate angiogenesis. In conditions like cancer, there is an upregulation and over-expression of ANG-2 [25].…”

Use of Antiangiogenic Therapies in Pediatric Solid Tumors

“…All this has led to the development of Ang2 inhibitors (PF-4856884) and Tie2 inhibitors (CE-245677) [ 24 ]. The role of Ang1 in tumor angiogenesis is unclear, since its overexpression seems to have either proangiogenic and protumor effect or antiangiogenic and antitumor effect depending on the specific type of cancer [ 35 ]. In any case, the results of simultaneously inhibiting Ang1 and Ang2 with inhibitors such as trebananib and AMG-780 are promising [ 24 , 34 , 36 ].…”

Exploring microRNA target genes and identifying hub genes in bladder cancer based on bioinformatic analysis

“…VEGFA is a member of the VEGF growth factor family, which can promote the proliferation and migration of vascular endothelial cells. VEGFA is significantly upregulated in many cancers and is essential for tumour proliferation, invasion and metastasis [ 34 , 35 ]. VCL is a cytoskeletal protein associated with cell–cell and cell–matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane.…”