Huizhi Sun1, Nan Yao1, Siqi Cheng1, Linqi Li1, Shiqi Liu1, Zhao Yang1, Guanjie Shang1, Danfang Zhang1,2, Zhi Yao1,3. 1. Department of Pathology, Tianjin Medical University, Tianjin 300070, China. 2. Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300070, China. 3. Department of Immunology, Tianjin Medical University, Tianjin 300070, China.
Abstract
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 with VM. In this study, triple-negative breast cancer (TNBC) enriched with CSCs was used to investigate the relationship between VM and 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-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. RESULTS: 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. CONCLUSIONS: 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.
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 with VM. In this study, triple-negative breast cancer (TNBC) enriched with CSCs was used to investigate the relationship between VM and 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-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. RESULTS: 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. CONCLUSIONS: 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.
Entities:
Keywords:
ALDH1; CD133; Vasculogenic mimicry; cancer stem-like cells; triple-negative breast cancer
Authors: Randolph S Watnick; Yi-Ning Cheng; Annapoorni Rangarajan; Tan A Ince; Robert A Weinberg Journal: Cancer Cell Date: 2003-03 Impact factor: 31.743
Authors: Robert Folberg; Zarema Arbieva; Jonas Moses; Amin Hayee; Tone Sandal; Shrihari Kadkol; Amy Y Lin; Klara Valyi-Nagy; Suman Setty; Lu Leach; Patricia Chévez-Barrios; Peter Larsen; Dibyen Majumdar; Jacob Pe'er; Andrew J Maniotis Journal: Am J Pathol Date: 2006-10 Impact factor: 4.307
Authors: A J Maniotis; R Folberg; A Hess; E A Seftor; L M Gardner; J Pe'er; J M Trent; P S Meltzer; M J Hendrix Journal: Am J Pathol Date: 1999-09 Impact factor: 4.307
Authors: Elisabeth A Seftor; Paul S Meltzer; Gina C Schatteman; Lynn M Gruman; Angela R Hess; Dawn A Kirschmann; Richard E B Seftor; Mary J C Hendrix Journal: Crit Rev Oncol Hematol Date: 2002-10 Impact factor: 6.312