Angiogenesis and vasculogenic mimicry as therapeutic targets in ovarian cancer

Abstract

Tumor angiogenesis is an essential process for growth and metastasis of cancer cells as it supplies tumors with oxygen and nutrients. During tumor angiogenesis, many pro-angiogenic factors are secreted by tumor cells to induce their own vascularization via activation of pre-existing host endothelium. However, accumulating evidence suggests that vasculogenic mimicry (VM) is a key alternative mechanism for tumor vascularization when tumors are faced with insufficient supply of oxygen and nutrients. VM is a tumor vascularization mechanism in which tumors create a blood supply system, in contrast to tumor angiogenesis mechanisms that depend on pre-existing host endothelium. VM is closely associated with tumor progression and poor prognosis in many cancers. Therefore, inhibition of VM may be a promising therapeutic strategy and may overcome the limitations of anti-angiogenesis therapy for cancer patients. In this review, we provide an overview of the current anti-angiogenic therapies for ovarian cancer and the current state of knowledge regarding the links between microRNAs and the VM process, with a focus on the mechanism that regulates associated signaling pathways in ovarian cancer. Moreover, we discuss the potential for VM as a therapeutic strategy against ovarian cancer. [

Vasculogenic mimicry, a negative indicator for progression free survival of lung adenocarcinoma irrespective of first line treatment and epithelial growth factor receptor mutation status

“…In theory, chemotherapy or targeted therapy combined with anti-VM should be a good strategy for this kind of disease. However, at present, anti-VM only stays at the stage of preclinical pharmacology and early clinical research, and there is no reliable evidence to support anti-VM [ 38 ]. It is expected that more research will focus on this field, so that anti-VM combined with current strategies can bring promising benefits to such patients.…”

MicroRNA 34a–AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells

“…In addition, many studies provide evidence that VM serves as a key alternative process for tumor neovascularization under an insufficient blood supply of oxygen and nutrients to the tumor tissue. VM is an alternative tumor vascularization mechanism that is directly built inside tumor cells to provide them with nutrients, which differs from angiogenesis via activation of the pre-existing host endothelium [ 10 , 11 , 39 ]. Thus, VM targeting may represent a promising therapeutic strategy and overcome the limitations of anti-angiogenic treatment of cancer patients.…”

“…Vasculogenic mimicry (VM) refers to a blood supply system that is formed in the tumor cells themselves, and not by vascular endothelial cells, such as in angiogenesis. These systems appear in malignant tumors and contribute to an aggressive disease, rapid tumor growth, and a poor prognosis [ 8 , 9 , 10 , 11 ]. It has been identified that various factors can regulate VM, including vascular endothelial cadherin, ephrin type-A receptor 2, focal adhesion kinase, extracellular signal-regulated kinase, and matrix metalloproteinase (MMP) [ 11 , 12 , 13 ].…”

“…These systems appear in malignant tumors and contribute to an aggressive disease, rapid tumor growth, and a poor prognosis [ 8 , 9 , 10 , 11 ]. It has been identified that various factors can regulate VM, including vascular endothelial cadherin, ephrin type-A receptor 2, focal adhesion kinase, extracellular signal-regulated kinase, and matrix metalloproteinase (MMP) [ 11 , 12 , 13 ]. Interestingly, epithelial–mesenchymal transition (EMT)-related regulatory factors are upregulated in tumor cells with VM formation and are shown to play a key role in VM formation [ 14 ].…”

“…MicroRNAs (miRNAs) are endogenous non-coding RNAs composed of 18–24 nucleotides, which play an essential role in biological processes by regulating gene expression [ 10 , 11 ]. As key regulators of gene expression, miRNAs are widely implicated in metastasis, tumorigenesis, and drug resistance [ 21 , 22 ].…”