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

Sun Huizhi, Yao Nan, Cheng Siqi, Li Linqi, Liu Shiqi, Yang Zhao, Shang Guanjie, Zhang Danfang, Yao Zhi
2019 Cancer Biology and Medicine  
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 with VM. In this study, triple-negative breast cancer (TNBC) enriched with CSCs was used to investigate the relationship between VM and CSCs. The expression of several CSC markers was detected by immunohistochemistry in 100 human breast cancer samples. The
more » ... nical significance of CSC markers and the relationship between VM, CSCs, breast cancer subtypes, and VM-associated proteins were analyzed. CD133+ and ALDH+ human and mouse TNBC cells were isolated by FACS to examine the ability of VM formation and the spatial relationship between VM and CSCs. CSCs were associated with TNBC subtype and VM in human invasive breast cancer. CSCs in TNBC MDA-MB-231 cells formed 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 3D reconstructed blood supply system in human TNBC grafts. The CD133+ and ALDH+ cells isolated from TA2 mouse breast cancer formed more VM channels in vivo. CSCs line VM channels directly. Additionally, CSCs provide more VM-related molecules to synergize VM formation. The signaling pathways that control CSC differentiation may also be potential treatment targets for TNBC.
doi:10.20892/j.issn.2095-3941.2018.0209 pmid:31516750 pmcid:PMC6713644 fatcat:kdgy3pmrhvfknb4ivsqg353vhq