TY - JOUR

T1 - Tumor endothelial marker 8 promotes cancer progression and metastasis

AU - Høye, Anette M.

AU - Tolstrup, Sofie D.

AU - Horton, Edward R.

AU - Nicolau, Monica

AU - Frost, Helen

AU - Woo, Jung H.

AU - Mauldin, Jeremy P.

AU - Frankel, Arthur E.

AU - Cox, Thomas R.

AU - Erler, Janine T.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Cancer

KW - Metastasis

KW - Tumor endothelial marker 8

U2 - 10.18632/oncotarget.25734

DO - 10.18632/oncotarget.25734

M3 - Journal article

C2 - 30046396

AN - SCOPUS:85049739088

VL - 9

SP - 30173

EP - 30188

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 53

ER -