Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis

Weiying Zhou; Miranda Y Fong; Yongfen Min; George Somlo; Liang Liu; Melanie R Palomares; Yang Yu; Amy Chow; Sean Timothy Francis O'Connor; Andrew R Chin; Yun Yen; Yafan Wang; Eric G Marcusson; Peiguo Chu; Jun Wu; Xiwei Wu; Arthur Xuejun Li; Zhuo Li; Hanlin Gao; Xiubao Ren; Mark P Boldin; Pengnian Charles Lin; Shizhen Emily Wang

doi:10.1016/j.ccr.2014.03.007

Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis

Cancer Cell. 2014 Apr 14;25(4):501-15. doi: 10.1016/j.ccr.2014.03.007.

Authors

Weiying Zhou¹, Miranda Y Fong², Yongfen Min³, George Somlo⁴, Liang Liu⁵, Melanie R Palomares⁶, Yang Yu⁵, Amy Chow², Sean Timothy Francis O'Connor², Andrew R Chin⁷, Yun Yen⁸, Yafan Wang⁹, Eric G Marcusson¹⁰, Peiguo Chu¹¹, Jun Wu¹², Xiwei Wu¹³, Arthur Xuejun Li¹⁴, Zhuo Li¹⁵, Hanlin Gao¹⁶, Xiubao Ren¹⁷, Mark P Boldin¹⁸, Pengnian Charles Lin³, Shizhen Emily Wang¹⁹

Affiliations

¹ Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; Department of Pharmacology, College of Pharmacy, The Third Military Medical University, Chongqing, 400038, China.
² Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
³ Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
⁴ Department of Medical Oncology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
⁵ Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; Department of Biotherapy and Key Laboratory of Cancer Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
⁶ Department of Medical Oncology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; Department of Population Sciences, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
⁷ Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; City of Hope Irell & Manella Graduate School of Biological Sciences, Duarte, CA 91010, USA.
⁸ Department of Molecular Pharmacology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; Core of Translational Research Laboratory, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
⁹ Core of Translational Research Laboratory, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
¹⁰ Oncology and Basic Mechanisms, Regulus Therapeutics, San Diego, CA 92121, USA.
¹¹ Department of Pathology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
¹² Department of Comparative Medicine, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
¹³ Core of Integrative Genomics, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
¹⁴ Department of Information Science, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
¹⁵ Core of Electron Microscopy, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
¹⁶ Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA; Core of Integrative Genomics, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
¹⁷ Department of Biotherapy and Key Laboratory of Cancer Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
¹⁸ Department of Molecular and Cellular Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA.
¹⁹ Department of Cancer Biology, City of Hope Beckman Research Institute and Medical Center, Duarte, CA 91010, USA. Electronic address: [email protected].

Abstract

Cancer-secreted microRNAs (miRNAs) are emerging mediators of cancer-host crosstalk. Here we show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in nonmetastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas inhibition of miR-105 in highly metastatic tumors alleviates these effects. miR-105 can be detected in the circulation at the premetastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology*
Cell Growth Processes / physiology
Cell Line, Tumor
Cell Movement
Endothelium, Vascular / metabolism
Endothelium, Vascular / pathology*
Female
Humans
MicroRNAs / genetics
MicroRNAs / metabolism*
Neoplasm Metastasis

Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis

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