Mechanisms of Vasculogenic Mimicry in Ovarian Cancer

Abstract

Solid tumors carry out the formation of new vessels providing blood supply for growth, tumor maintenance, and metastasis. Several processes take place during tumor vascularization. In angiogenesis, new vessels are derived from endothelial cells of pre-existing vessels; while in vasculogenesis, new vessels are formed de novo from endothelial progenitor cells, creating an abnormal, immature, and disorganized vascular network. Moreover, highly aggressive tumor cells form structures similar to vessels, providing a pathway for perfusion; this process is named vasculogenic mimicry (VM), where vessel-like channels mimic the function of vessels and transport plasma and blood cells. VM is developed by numerous types of aggressive tumors, including ovarian carcinoma which is the second most common cause of death among gynecological cancers. VM has been associated with poor patient outcome and survival in ovarian cancer, although the involved mechanisms are still under investigation. Several signaling molecules have an important role in VM in ovarian cancer, by regulating the expression of genes related to vascular, embryogenic, and hypoxic signaling pathways. In this review, we provide an overview of the current knowledge of the signaling molecules involved in the promotion and regulation of VM in ovarian cancer. The clinical implications and the potential benefit of identification and targeting of VM related molecules for ovarian cancer treatment are also discussed.

Vasculogenic mimicry in carcinogenesis and clinical applications

“…In glioblastomas, when there is insufficient blood supply in the tumor, glioblastoma stem-like cells express pro-vascular molecules such as EGFR, endothelium-associated genes including EphA2, Laminin 5γ2, and Neuropilin-2, leading to the de novo formation of blood vessels with GSCs as the lining cells of the luminal surface [41]. The patterned matrix type features tumor cells and tissue that are wrapped around by PAS-positive matrix proteins such as laminin, heparan sulfate proteoglycan, and collagens IV and VI [42]. This type has neither the tubular nor ultrastructural characteristics of blood vessels, which could be precisely described by its extravascular matrix patterns [40].…”

SOX7 blocks vasculogenic mimicry in oral squamous cell carcinoma

“…Mitra et al, recently found that phosphorylation of EphA2 was signi cantly associated with the occurrence of VM in invasive breast carcinoma [40]. Co-localization of VE-cadherin with EphA2 is reported to induce the activation of MMPs, resulting in matrix remodeling and VM channel formation [12,15,41]. These ndings suggest that VE-cadherin, EphA2, and MMPs are important VM-modulating genes.…”

SOX7 Blocks Vasculogenic Mimicry in Oral Squamous Cell Carcinoma

“…Mitra et al, recently found that phosphorylation of EphA2 was signi cantly associated with the occurrence of VM in invasive breast carcinoma [42]. Co-localization of VE-cadherin with EphA2 is reported to induce the activation of MMPs, resulting in matrix remodeling and VM channel formation [12,15,43]. These ndings suggest that VE-cadherin, EphA2, and MMPs are important VM-modulating genes.…”