Stem-like Human Breast Cancer Cells Initiate Vasculogenic Mimicry on Matrigel

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Vasculogenic mimicry (VM), referring to vasculogenic structures lined by tumor cells, can be distinguished from angiogenesis, and is responsible for the aggressiveness and metastatic potential of tumors. HCC1937/p53 cells were derived from triple-negative breast cancer (TNBC), and used to investigate the roles of breast cancer stem cells (CSCs) in the formation of VM. HCC1937/p53 cells formed mesh-like structures on matrigel culture in which expression of VM-related genes, vascular endothelial (VE)-cadherin, matrix metalloproteinase (MMP)-2 and MMP-9 was confirmed by droplet digital polymerase chain reaction (PCR). In immunofluorescence microscopy, aldehyde dehydrogenase (ALDH)1A3⁺ cells with properties of CSCs or progenitors and GATA binding protein 3 (GATA3)⁺ cells with more differentiated characteristics were localized in the bridging region and aggregated region of VM structures, respectively. In fluorescence-activated cell sorting analysis, ALDH⁺ cells, considered to be a subpopulation of CSCs sorted by the aldefluor assay, exhibited marked VM formation on matrigel in 24 hr, whereas ALDH⁻ cells did not form VM, indicating possible roles of CSCs in VM formation. The stem-like cancer cells resistant to p53-induced apoptosis, which expressed a high rate of ALDH1A3 and Sex-determining region Y (SRY)-box binding protein-2 (Sox-2), completed VM formation much faster than the control. These findings may provide clues to elucidate the significance of VM formed by treatment-resistant CSCs in the metastatic potential and poor prognosis associated with TNBC.