Epithelial Mesenchymal Transition and Vascular Mimicry in Breast Cancer Stem Cells

Abstract

Vasculogenic mimicry (VM), a newly defined pattern of tumor microvascularization differs from angiogenesis and vasculogenesis in its noninvolvement of endothelial cells, by which highly aggressive tumor cells can form vessel-like structures themselves, because of their high plasticity. The presence of VM has been shown to be strongly associated with a poor prognosis in several types of cancer, but biological features of tumor cells that form VM remains unknown. Human breast cancer, characterized by a group of highly heterogeneous lesions, is the most common cancer in women and one of the leading causes of cancer-related deaths worldwide. The epithelialmesenchymal transition (EMT) state in breast cancer has been associated with cancer stem cell (CSC) properties, self-renewal capabilities, resistance to conventional therapies, and a tendency for posttreatment recurrence. With increasing knowledge about cancer stem cell phenotypes and functions, they are implicated in VM formation. Studies also indicate that EMT is relevant to the acquisition and maintenance of stem cell-like characteristics and is involved in VM. This review discusses the correlation between CSCs, EMT, and VM formation with a focus on breast cancer. Also, the signalling molecules and pathways involved in VM and some recently defined direct VM targeting strategies in breast cancer are reviewed here.

Role of p38γ MAPK in regulation of EMT and cancer stem cells

“…p38γ MAPK-enhanced EMT is accompanied by an increase in cancer stem cells (CSCs), which was consistent with the findings showing that induction of EMT is associated with the presence of cancer stem cells (CSCs) [13, 32]. We further delineated a down-stream signaling pathway that may mediate the action of p38γ MAPK (Fig.…”

“…EMT also plays a crucial role for cancer progression, and contributes to the dissemination of cancer cells from solid tumors and the formation of detectable metastases [11]. EMT has also been implicated in therapy resistance, relapse, immune escape, and maintenance of cancer stem cell properties, such as self-renewal capacity [12, 13]. Understanding the complex events that lead to the EMT will therefore help to design new therapies against metastatic breast cancer.…”

ZEB1‐mediated vasculogenic mimicry formation associates with epithelial–mesenchymal transition and cancer stem cell phenotypes in prostate cancer

“…Notably, VM is a known novel vascular network pattern that is formed by tumour cells but not endothelial cells in various cancers, including breast cancer, glioma and PCa . The VM structure was firstly reported by Maniotis et al, and the VM is formed by aggressive tumour cells gaining the characteristics of transdifferentiation and acquiring endothelial cell behaviour to access nutrition and initiate metastasis .…”

The relationship between vasculogenic mimicry and epithelial‐mesenchymal transitions

“…Epithelial-mesenchymal transition-like phenotype can be induced by hypoxic microenvironment which is of great significance in inducing VM in cancer cells. This phenotype is characterized with increased motility and invasiveness, and fibroblast-like cell-cell adhesion, which allows the cells to break free from the primary tumour site and metastasize at distant sites [26,27]. Moreover, it is demonstrated that EMT-related transcription factors are up-regulated in VM-forming tumour cells.…”