Publication: Tumor endothelial marker 8 promotes cancer progression and metastasis

Thomas R. Cox, Jul 2018

Tumor endothelial marker 8 promotes cancer progression and metastasis

Our new paper has just been published in Oncotarget. In this study, we show that Tumor endothelial marker 8 (TEM8) regulates the expression of multiple genes. In particular, we observed that the most common expression changes conserved between breast and colorectal cancer are involved in regulation of the cell cycle. In line with the microarray results we show that TEM8 regulates cancer cell proliferation and primary tumor growth. Since TEM8 KO tumors presented with fewer blood vessels we hypothesize that TEM8 contributes to the regulation of angiogenesis, likely by being secreted by cancer cells to alter endothelial cell migration and thereby supporting growth of the tumor. Moreover, we confirm that TEM8 is an important player in driving tumor cell invasion and metastatic dissemination in breast cancer.

Tumor endothelial marker 8 promotes cancer progression and metastasis

Proposed mechanism behind the impact of TEM8 on breast and CRC cancer progression.

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.

Links

View the article on the Oncotarget website
Download the PDF here

Citation

Hoye et al. Tumor endothelial marker 8 promotes cancer progression and metastasis
Oncotarget (2019) | doi: 10.18632/oncotarget.25734

Key Words

Angiogenesis; Cancer; Metastasis, Tumor Endothelial Marker 8

Funding

We thank the Biocentre animal facility and BRIC histology core facility for assistance. This work was supported by the Danish Cancer Society (R-56-A-3342-12-S2) (AMH, ERH), an EMBO Long-Term Fellowship (ALTF 922-2016) (ERH), a Susan G. Komen Career Catalyst Grant (CCR17483294) (TRC), the National Health and Medical Research Council (NHMRC) Australia (TRC), and the Novo Nordisk Foundation with a Hallas Møller Stipend (JTE).