Cancer stem-like cells directly participate in vasculogenic mimicry channels in triple-negative breast cancer

Objective: Vasculogenic mimicry (VM) channels that are lined by tumor cells are a functional blood supply in malignant tumors.However, the role of VM-initiating cells remains poorly understood. Cancer stem-like cells (CSCs) are positively correlated withVM. In this study, triple-negative breast cancer (TNBC) enriched with CSCs was used to investigate the relationship between VMand CSCs. Methods: The expression of several CSC markers was detected by immunohistochemistry in 100 human breast cancer samples.The clinical significance of CSC markers and the relationship between VM, CSCs, breast cancer subtypes, and VM-associatedproteins were analyzed. CD133+ and ALDH+ human and mouse TNBC cells were isolated by FACS to examine the ability of VMformation and the spatial relationship between VM and CSCs. Results: CSCs were associated with TNBC subtype and VM in human invasive breast cancer. CSCs in TNBC MDA-MB-231 cellsformed more VM channels and expressed more molecules promoting VM than the non-TNBC MCF-7 cells in vitro. MDA-MB-231 cells that encircled VM channels on Matrigel expressed CD133. Moreover, CSCs were located near VM channels in the 3Dreconstructed blood supply system in human TNBC grafts. The CD133+ and ALDH+ cells isolated from TA2 mouse breast cancerformed more VM channels in vivo. Conclusions: CSCs line VM channels directly. Additionally, CSCs provide more VM-related molecules to synergize VMformation. The signaling pathways that control CSC differentiation may also be potential treatment targets for TNBC.