Oncotarget

Research Papers:

Tumor endothelial marker 8 promotes cancer progression and metastasis

Anette M. Høye, Sofie D. Tolstrup, Edward R. Horton, Monica Nicolau, Helen Frost, Jung H. Woo, Jeremy P. Mauldin, Arthur E. Frankel, Thomas R. Cox, Janine T. Erler _

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Oncotarget. 2018; 9:30173-30188. https://doi.org/10.18632/oncotarget.25734

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Abstract

Anette M. Høye1,*, Sofie D. Tolstrup1,*, Edward R. Horton1, Monica Nicolau1, Helen Frost1, Jung H. Woo2, Jeremy P. Mauldin2, Arthur E. Frankel3, Thomas R. Cox1,4 and Janine T. Erler1

1Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen (UCPH), Copenhagen, Denmark

2Baylor Scott and White Health, Temple, TX, USA

3University of South Alabama Mitchell Cancer Institute, Mobile, AL, USA

4The Garvan Institute of Medical Research and The Kinghorn Cancer Centre, Cancer Division, St Vincent’s Clinical School, Faculty of Medicine, UNSW, Sydney, Australia

*These authors contributed equally to this work

Correspondence to:

Janine T. Erler, email: janine.erler@bric.ku.dk

Keywords: tumor endothelial marker 8; cancer; angiogenesis; metastasis

Received: April 19, 2017     Accepted: June 22, 2018     Published: July 10, 2018

ABSTRACT

Every year more than 8 million people suffer from cancer-related deaths worldwide [1]. Metastasis, the spread of cancer to distant sites, accounts for 90% of these deaths. A promising target for blocking tumor progression, without causing severe side effects [2], is Tumor Endothelial Marker 8 (TEM8), an integrin-like cell surface protein expressed predominantly in the tumor endothelium and in cancer cells [3, 4]. Here, we have investigated the role of TEM8 in cancer progression, angiogenesis and metastasis in invasive breast cancer, and validated the main findings and important results in colorectal cancer. We show that the loss of TEM8 in cancer cells results in inhibition of cancer progression, reduction in tumor angiogenesis and reduced metastatic burden in breast cancer mouse models. Furthermore, we show that TEM8 regulates cancer progression by affecting the expression levels of cell cycle-related genes. Taken together, our findings may have broad clinical and therapeutic potential for breast and colorectal primary tumor and metastasis treatment by targeting TEM8.


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