Molecular mechanisms of Thrombospondin-2 modulates tumor vasculogenic mimicry by PI3K/AKT/mTOR signaling pathway

• Published in: Biomedicine & pharmacotherapy Vol. 167; p. 115455
• Main Authors: Huang, Ju, Wang, Congcong, Hou, Yixuan, Tian, Yuanyuan, Li, Yanru, Zhang, Haiying, Zhang, Lihong, Li, Wei
• Format: Journal Article
• Language: English
• Published: Elsevier Masson SAS 01-11-2023; Elsevier
• Subjects: Angiogenesis; CD36; PI3K/AKT/mTOR signaling pathway; Thrombospondin 2; Vasculogenic mimicry; PAS; IHC; RTK; DN; THBS2; SHP-1; EphA2; DFS; Angiogenesis; CAFs; PI3K; VE-cadherin; VEGFR; TIMP2; CD36; EC; CSCs; Vasculogenic mimicry; OS; MMPs; VEGF-A; EMT; ECM; Thrombospondin 2; PI3K/AKT/mTOR signaling pathway; EET; VM
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.115455

Vasculogenic mimicry (VM) differs from the classical tumor angiogenesis model. VM does not depend on endothelial cells; instead, highly aggressive tumor cells mimic endothelial cells to form a vascular-like channel structure. VM mediated by tumor cells is significantly and positively associated with a poor prognosis and low survival rates in patients with highly aggressive cancer. In the treatment of highly aggressive malignancies, the presence of VM is considered an important reason for the unsatisfactory clinical efficacy of anti-tumor–angiogenesis therapy (e.g., therapy targeting vascular endothelial growth factor A). Many targeted therapeutic drugs based on traditional tumor blood vessels have been used clinically. Although some progress has been made in certain tumors, problems such as drug resistance have restricted the expected therapeutic effects. Thrombospondin 2 (THBS2) is one of the most important genes associated with angiogenesis, and this gene exerts angiogenesis-related functions through the PI3K/AKT signaling pathway. Although the PI3K/AKT/mTOR signaling pathway is closely related to the progression of VM, the mechanism by which the promising biomarker THBS2 participates in and regulates tumor VM by activating the PI3K/AKT/mTOR signaling pathway is unclear. In this review, we analyze the monomer structure and biological activity of THBS2, the structure and potential synthesis mechanisms of VM, and the complex mechanisms between THBS2, the PI3K/AKT/mTOR signaling pathway, and VM.
•Thrombospondin-2 (THBS2) is highly expressed in various tumors and participates in angiogenesis of various tumors by activating the PI3K/AKT signaling pathway.•The PI3K/AKT/mTOR signaling pathway is closely related to tumor VM formation.•Mechanism and key molecules in tumor VM formation.•In this review, we hypothesize the association between THBS2 and tumor VM formation.•Clinical significance and limitations of VM in tumor treatment.