Abstract PR1: Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis

Abstract

Abstract Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression towards metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we have tested whether platelets present in the bloodstream can provide a signaling platform for cancer cells outside of the primary tumor and influence the metastatic potential of tumor cells. We show that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGFß and direct platelet-tumor cell contacts synergistically activate the TGFß/Smad and NF-κB pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-κB signaling in cancer cells or ablation of TGFß1 expression solely in platelets protects against lung metastasis in vivo. Thus, our study establishes platelets as a major and critical source of TGFß bioavailable to cancer cells in the circulation, and reveals that the metastatic potential of tumor cells continues to evolve outside the primary tumor site, in response to tumor-host interactions in the bloodstream. Platelet-tumor cell interactions and the signaling pathways that they trigger are therefore crucial determinants of cancer metastasis and potential targets for anti-metastatic therapies. This abstract is also presented as Poster A9. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr PR1.