Significance and therapeutic implications of endothelial progenitor cells in angiogenic-mediated tumour metastasis

Abstract

Cancer conveys profound social and economic consequences throughout the world. Metastasis is responsible for approximately 90% of cancer-associated mortality and, when it occurs, cancer becomes almost incurable. During metastatic dissemination, cancer cells pass through a series of complex steps including the establishment of tumour-associated angiogenesis. The human endothelial progenitor cells (hEPCs) are a cell population derived from the bone marrow which are required for endothelial tubulogenesis and neovascularization. They also express abundant inflammatory cytokines and paracrine angiogenic factors. Clinically hEPCs are highly correlated with relapse, disease progression, metastasis and treatment response in malignancies such as breast cancer, ovarian cancer and non-small-cell lung carcinoma. It has become evident that the hEPCs are involved in the angiogenesis-required progression and metastasis of tumours. However, it is not clear in what way the signalling pathways, controlling the normal cellular function of human BM-derived EPCs, are hijacked by aggressive tumour cells to facilitate tumour metastasis. In addition, the actual roles of hEPCs in tumour angiogenesis-mediated metastasis are not well characterised. In this paper we reviewed the clinical relevance of the hEPCs with cancer diagnosis, progression and prognosis. We further summarised the effects of tumour microenvironment on the hEPCs and underlying mechanisms. We also hypothesized the roles of altered hEPCs in tumour angiogenesis and metastasis. We hope this review may enhance our understanding of the interaction between hEPCs and tumour cells thus aiding the development of cellular-targeted anti-tumour therapies.

Pro-apoptotic effect of TRAIL-transfected endothelial progenitor cells on glioma cells

“…Many studies investigated the relationship between EPCs and tumors ( 22 ). Most previous studies focused on anti-angiogenic treatment by suppressing the mobilization and homing of EPCs to tumors ( 20 ). Only a few studies used EPCs as a vector for treatment ( 21 ).…”

“…Owing to these characteristics, EPCs have the potential to be involved in anti-tumor therapies. Most previous studies explored anti-angiogenic treatment by suppressing the mobilization and homing of EPCs to tumors ( 20 ). Increasing attention has been paid to the use of EPCs as a vector for treatment ( 21 , 22 ).…”

Hematopoietic Substrate-1-Associated Protein X-1 Regulates the Proliferation and Apoptosis of Endothelial Progenitor Cells Through Akt Pathway Modulation

“…Endothelial precursor cells (EPCs) have been reported to be involved in postnatal vasculogenesis in both physiological and pathological conditions in recent years . Growing evidence suggests the contribution of EPCs in diseases such as ischemia, stroke, retinopathy, peripheral vascular disease, and, especially, tumor neovasculogenesis . Although there are plenty of research works on the identification and function of EPCs, their survival mechanism still remains unclear at the current stage.…”

Effects of Notch signalling pathway on the relationship between vascular endothelial dysfunction and endothelial stromal transformation in atherosclerosis

“…All receptors and ligands are transmembrane proteins, and adjacent cells can pass through the binding of the receptor to the ligand. Notch1, Notch3, Notch4, Delta-like4, Jagged1 and Jagged2 were expressed on the arterial endothelium [13]. The Notch signalling pathway is a conserved and important signal transduction pathway that affects cell fate, which involves almost all cell proliferation and differentiation activities, and plays an important role in regulating cell differentiation, proliferation and apoptosis, and a series of physiological pathologies [14].…”