Høye Anette M, Tolstrup Sofie D, Horton Edward R, Nicolau Monica, Frost Helen, Woo Jung H, Mauldin Jeremy P, Frankel Arthur E, Cox Thomas R, Erler Janine T
Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen (UCPH), Copenhagen, Denmark.
Baylor Scott and White Health, Temple, TX, USA.
Oncotarget. 2018 Jul 10;9(53):30173-30188. doi: 10.18632/oncotarget.25734.
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.
全球每年有超过800万人死于癌症相关疾病[1]。转移，即癌症扩散至远处部位，占这些死亡人数的90%。肿瘤内皮标志物8（TEM8）是一种主要在肿瘤内皮和癌细胞中表达的整合素样细胞表面蛋白，是一个有前景的、不会引起严重副作用的阻断肿瘤进展的靶点[2]。在此，我们研究了TEM8在浸润性乳腺癌的癌症进展、血管生成和转移中的作用，并在结直肠癌中验证了主要发现和重要结果。我们发现，癌细胞中TEM8的缺失会抑制癌症进展、减少肿瘤血管生成并减轻乳腺癌小鼠模型中的转移负担。此外，我们还表明，TEM8通过影响细胞周期相关基因的表达水平来调节癌症进展。综上所述，我们的研究结果可能通过靶向TEM8对乳腺癌和结直肠癌的原发性肿瘤及转移治疗具有广泛的临床和治疗潜力。
