Research Papers:

Claudin-4 is required for vasculogenic mimicry formation in human breast cancer cells

Yong-Feng Cui, An-Heng Liu, Dai-Zhi An, Ru-Bao Sun, Yun Shi, Yun-Xiang Shi, Miao Shi, Qiang Zhang, Li-Li Wang, Qiong Feng, Gui-Lan Pan and Qiang Wang _

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Oncotarget. 2015; 6:11087-11097. https://doi.org/10.18632/oncotarget.3571

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Yong-Feng Cui1,*, An-Heng Liu2,*, Dai-Zhi An1,*, Ru-Bao Sun1, Yun Shi1, Yun-Xiang Shi3, Miao Shi1, Qiang Zhang1, Li-Li Wang1, Qiong Feng3, Gui-Lan Pan3 and Qiang Wang1

1 Center of Hygiene Assessment and Research, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China

2 Cardiovascular Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China

3 Department of Physiology, BaoTou Medical College, Inner Mongolia University of Science and Technology, Baotou, China

* These authors contributed equally to this work

Correspondence to:

Qiang Wang, email:

Keywords: claudins, tight junction, vasculogenic mimicry, aggressive breast cancer

Received: February 03, 2015 Accepted: February 22, 2015 Published: March 14, 2015


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.

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