title: Claudin-4 is required for vasculogenic mimicry formation in human breast cancer cells.
abstract: Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. Claudins are aberrantly expressed in aggressive breast cancer. However, the relationship between claudins and VM formation is not clear. We examined VM in two human breast cancer cell lines with different aggressive capabilities (MDA-MB-231 and MCF-7 cells) and one human umbilical vein endothelial cell line (HUVEC). Both HUVEC and MDA-MB-231 cells formed vascular channels in Matrigel cultures, while MCF-7 cells did not. Western blot analysis revealed a possible correlation between claudin-4 and -6 expression in breast cancer cell lines and tumor aggressiveness, with protein levels correlating with the ability to form vascular channels. Treatment of MDA-MB-231 and HUVEC cells with claudin-4 monoclonal antibodies completely inhibited the ability of cells to form vascular channels. Moreover, knockdown of claudin-4 by short hairpin RNA completely inhibited tubule formation in MDA-MB-231 cells. Overexpression of claudin-4 in MCF-7 cells induced formation of vascular channels. Immunocytochemistry revealed that membranous claudin-4 protein was significantly associated with vascular channel formation. Collectively, these results indicate that claudin-4 may play a critical role in VM in human breast cancer cells, opening new opportunities to improve aggressive breast cancer therapy.
authors: Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors: Yong-Feng
authors: YF
authors: Cui
authors: Cardiovascular Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.
authors: An-Heng
authors: AH
authors: Liu
authors: Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors: Dai-Zhi
authors: DZ
authors: An
authors: Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors: Ru-Bao
authors: RB
authors: Sun
authors: Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors: Yun
authors: Y
authors: Shi
authors: Department of Physiology, BaoTou Medical College, Inner Mongolia University of Science and Technology, Baotou, China.
authors: Yun-Xiang
authors: YX
authors: Shi
authors: Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors: Miao
authors: M
authors: Shi
authors: Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors: Qiang
authors: Q
authors: Zhang
authors: Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors: Li-Li
authors: LL
authors: Wang
authors: Department of Physiology, BaoTou Medical College, Inner Mongolia University of Science and Technology, Baotou, China.
authors: Qiong
authors: Q
authors: Feng
authors: Department of Physiology, BaoTou Medical College, Inner Mongolia University of Science and Technology, Baotou, China.
authors: Gui-Lan
authors: GL
authors: Pan
authors: Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors: Qiang
authors: Q
authors: Wang
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D062506:Claudin-4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D061307:Human Umbilical Vein Endothelial Cells / Q000473:pathology*; D006801:Humans; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D062506:Claudin-4; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: aggressive breast cancer; claudins; tight junction; vasculogenic mimicry