Epithelial-to-endothelial transition and cancer stem cells: two cornerstones of vasculogenic mimicry in malignant tumors

Abstract

Vasculogenic mimicry (VM) is a functional microcirculation pattern in malignant tumors accompanied by endothelium-dependent vessels and mosaic vessels. VM has been identified in more than 15 solid tumor types and is associated with poor differentiation, late clinical stage and poor prognosis. Classic anti-angiogenic agents do not target endothelium-dependent vessels and are not efficacious against tumors exhibiting VM. Further insight into the molecular signaling that triggers and promotes VM formation could improve anti-angiogenic therapeutics. Recent studies have shown that cancer stem cells (CSCs) and epithelium-to-endothelium transition (EET), a subtype of epithelial-to-mesenchymal transition (EMT), accelerate VM formation by stimulating tumor cell plasticity, remodeling the extracellular matrix (ECM) and connecting VM channels with host blood vessels. VM channel-lining cells originate from CSCs due to expression of EMT inducers such as Twist1, which promote EET and ECM remodeling. Hypoxia and high interstitial fluid pressure in the tumor microenvironment induce a specific type of cell death, linearly patterned programmed cell necrosis (LPPCN), which spatially guides VM and endothelium-dependent vessel networks. This review focuses on the roles of CSCs and EET in VM, and on possible novel anti-angiogenic strategies against alternative tumor vascularization.

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

“…However, EMT also contributes toward VM formation by stimulating tumor cell plasticity and degrading the extracellular matrix (EXCM) to mimic endothelial cells and to form VM channels. 29,39 In this study, we verified that AuNPs inhibited the expression of c-Myc and regulated the progression of EMT. MMP-2 is involved in the breakdown of EXCM and plays an important role in angiogenesis within tumors, 40 and hypoxia can activate this progression to facilitate tumor angiogenesis, invasion and metastasis.…”

The Expression and Functional Significance of Runx2 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry and Epithelial–Mesenchymal Transition

“…The transition into endothelial cells is similar to an epithelial-mesenchymal cell transition. EMT is a process by which epithelial cells lose their epithelial characteristics and gain mesenchymal characteristics, acquiring the ability to invade and metastasize [28,29]. During EMT, the expression of epithelial markers such as E-cadherin are downregulated and the expression of mesenchymal markers such as Vimentin is upregulated [22,30].…”

Activation of Notch pathway is linked with epithelial-mesenchymal transition in prostate cancer cells

“…It has been reported that EMT is associated with CSCs in human cancers. 52 CSCs possess the ability to self-renew and differentiate. 53 Moreover, CSCs have been validated and isolated from many human cancers including prostate cancer.…”