Inhibition of tissue factor signaling suppresses tumor growth

Henri H. Versteeg, Florence Schaffner, Marjolein Kerver, Helle H. Petersen, Jasimuddin Ahamed, Brunhilde Felding-Habermann, Yoshikazu Takada, Barbara M. Mueller, Wolfram Ruf

研究成果: 雜誌貢獻文章同行評審

259 引文 斯高帕斯(Scopus)

摘要

Coagulation activation by tissue factor (TF) is implicated in cancer progression, cancer-associated thrombosis and metastasis. The role of direct TF signaling pathways in cancer, however, remains incompletely understood. Here we address how TF contributes to primary tumor growth by using a unique pair of isotype-matched antibodies that inhibit either coagulation (monoclonal antibody [Mab]-5G9) or direct signaling (Mab-10H10). We demonstrate that the inhibitory antibody of direct TF-VIIa signaling not only blocks TF-VIIa mediated activation of PAR2, but also disrupts the interaction of TF with integrins. In epithelial and TF-expressing endothelial cells, association of TF with β1 integrins is regulated by TF extracellular ligand binding and independent of PAR2 signaling or proteolytic activity of VIIa. In contrast, α3β1 integrin association of TF is constitutive in breast cancer cells and blocked by Mab-10H10 but not by Mab-5G9. Mab-5G9 has antitumor activity in vivo, but we show here that Mab-10H10 is at least as effective in suppressing human xenograft tumors in 2 different models. Breast tumor growth was also attenuated by blocking PAR2 signaling. These results show that tumor cell TF-PAR2 signaling is crucial for tumor growth and suggest that anti-TF strategies can be applied in cancer therapy with minor impairment of TF-dependent hemostatic pathways.

原文英語
頁(從 - 到)190-199
頁數10
期刊Blood
111
發行號1
DOIs
出版狀態已發佈 - 1月 1 2008
對外發佈

ASJC Scopus subject areas

  • 生物化學
  • 免疫學
  • 血液學
  • 細胞生物學

指紋

深入研究「Inhibition of tissue factor signaling suppresses tumor growth」主題。共同形成了獨特的指紋。

引用此