Vasculogenic mimicry in carcinogenesis and clinical applications

Abstract

Distinct from classical tumor angiogenesis, vasculogenic mimicry (VM) provides a blood supply for tumor cells independent of endothelial cells. VM has two distinct types, namely tubular type and patterned matrix type. VM is associated with high tumor grade, tumor progression, invasion, metastasis, and poor prognosis in patients with malignant tumors. Herein, we discuss the recent studies on the role of VM in tumor progression and the diverse mechanisms and signaling pathways that regulate VM in tumors. Furthermore, we also summarize the latest findings of non-coding RNAs, such as lncRNAs and miRNAs in VM formation. In addition, we review application of molecular imaging technologies in detection of VM in malignant tumors. Increasing evidence suggests that VM is significantly associated with poor overall survival in patients with malignant tumors and could be a potential therapeutic target.

Establishment and Characterization of Canine Mammary Gland Carcinoma Cell Lines With Vasculogenic Mimicry Ability in vitro and in vivo

“…Although we used markers and experiments from the literature (17,20,62), other markers may be used to confirm the tubularlike structures as VM. One limitation of our study was the absence of investigation of further markers related to VM, such as VE-cadherin, transforming growth factor-β1 (TGF-β1), and EpCam (14,17,19,63). The evaluation of these markers in future research may be valuable for a better characterization of VM markers in canine mammary gland tumors.…”

“…The presence of these vessels may be associated with a more aggressive tumor, a higher histopathological grade, shorter survival time, and a higher capacity of invasion and metastasis (14). The mechanisms involved in VM formation include the expression of markers related to epithelial-mesenchymal transition (EMT), stem cell properties, and hypoxia (14,17,18). EMT allows tumor cells to change their cytoskeleton in order to promote invasion and metastasis.…”

“…During tubular formation, aggressive cells express EMT markers, acquire plasticity, and form vascularlike structures (19). During these processes, proteins such as E-cadherin, occludin-1, and α-catenin zone are downregulated while VE-cadherin, fibronectin, cadherin-2, and vimentin are upregulated (14,(17)(18)(19). Some receptors are also involved in the signaling of the VM pathway, such as ephrin type A receptor 2 (EphA2), focal adhesion kinase (FAK), phosphotidylinositol-3-kinase (PI3K), matrix metalloproteinase (MMP), Notch, and hypoxia-inducible factor 1-alpha (HIF1-α).…”

SOX7 blocks vasculogenic mimicry in oral squamous cell carcinoma

“…Formed by the process of vasculogenic mimicry (VM), these structures consist of periodic acid-Schiff (PAS) + and CD31-negative basement membranes lined by tumor cells rather than endothelial cells [5]. VM has been vividly described in numerous types of malignant tumors and is closely associated with a poor clinical outcome [6][7][8]. Experimental evidence has con rmed a relationship between VM and tumor metastasis in a variety of cancer cell lines and has shown that tumor cells can form VM channels in Matrigel culture [9][10][11].…”

Crocetin suppresses angiogenesis through inhibiting Sonic hedgehog signaling pathway in gastric cancer

“…Moreover, VM is signi cantly correlated with poor prognosis of cancer patients [24] and has emerged as a new target for anti-tumor therapy [25]. Although there is no lack of research on signaling pathways associated with VM in highly aggressive malignant tumors [26], the role of Shh/Gli1 signaling in VM formation is rarely discussed.…”