Overview of advances in vasculogenic mimicry – a potential target for tumor therapy

Abstract

Vasculogenic mimicry (VM) describes the process utilized by highly aggressive cancer cells to generate vascular-like structures without the presence of endothelial cells. VM has been vividly described in various tumors and participates in cancer progression dissemination and metastasis. Diverse molecular mechanisms and signaling pathways are involved in VM formation. Furthermore, the patterning characteristics of VM, detected with molecular imaging, are being investigated for use as a tool to aid clinical practice. This review explores the most recent studies investigating the role of VM in tumor induction. Indeed, the recognition of these advances will increasingly affect the development of novel therapeutic target strategies for VM in human cancer.

Vasculogenic mimicry in carcinogenesis and clinical applications

“…Histologic and imaging characteristics of VM VM has been demonstrated as a potential indicator of the poor prognosis of patients with VM-positive tumors in many studies [3,16,20,26,100,102,103]. Immunohistochemistry (IHC) staining is currently the gold standard for VM diagnosis in malignant tumors.…”

“…Molecular imaging could be used to understand the biological processes of VM in living organisms. Interestingly, specific contrasting agents that can enter VM tubes and be detected by novel molecular imaging technologies can provide non-invasive imaging for a better way to detect VM in patients, which can guide treatment [20,106,107]. However, there are many challenges, such as absence of specific contrasting agent that could distinguish between blood vessels formed via VM or tumor angiogenesis, and the ability of different malignant tumors to form VM tubular structures is different.…”

“…In recent years, VM has been reported in a variety of malignant tumors, such as melanoma, glioblastoma, osteosarcoma, hepatocellular carcinoma (HCC), breast cancer, lung cancer, gastric cancer, colorectal cancer, and prostate cancer [7][8][9][10][11][12][13][14][15][16][17][18][19]. VM has emerged as a promising new target for anti-tumor therapy [20,21]. There are several potential mechanisms of VM formation, such as epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) [22,23], and various signaling pathways that promote VM formation, including vascular endothelial (VE)-cadherin, erythropoietin-producing hepatocellular receptor A2 (EphA2), phosphatidyl inositol 3-kinase (PI3K), matrix metalloproteinases (MMPs), vascular endothelial growth factor receptor (VEGFR1), cyclic adenosine monophosphate (cAMP), focal adhesion kinase (FAK), and hypoxia inducible factor (HIF)-1a [24,25].…”

Investigation of the Prognostic Significance of Vasculogenic Mimicry and Its Inhibition by Sorafenib in Canine Mammary Gland Tumors

“…Vasculogenic mimicry (VM) is defined as a process used by highly aggressive neoplastic cells to generate vascularlike structures without the presence of endothelial cells (6). VM has been extensively described in various tumors and participates in tumor spread and metastasis (6)(7)(8)(9). Many signaling mechanisms are involved in the initiation of VM.…”

“…Many signaling mechanisms are involved in the initiation of VM. Molecules that are involved in this process are being investigated with the aim of developing new strategies for therapeutic targets against cancer (6). Although, the mechanism of VM is not yet clear, studies have found that the ERK-1/PI3K/MMP-2 signaling pathway may be critical.…”