Direct Signaling between Platelets and Cancer Cells Induces an Epithelial-Mesenchymal-Like Transition and Promotes Metastasis
Menée in vitro et in vivo, cette étude identifie un mécanisme de signalisation entre cellules cancéreuses et thrombocytes induisant une transition épithélio-mésenchymateuse et favorisant le processus métastatique
Interactions of cancer cells with the primary tumor microenvironment are important determinants of cancer progression toward metastasis but it is unknown whether additional prometastatic signals are provided during the intravascular transit to the site of metastasis. Here, we show that platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGF² and direct platelet-tumor cell contacts synergistically activate the TGF²/Smad and NF-ºB pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-ºB signaling in cancer cells or ablation of TGF²1 expression solely in platelets protects against lung metastasis in vivo. Thus, cancer cells rely on platelet-derived signals outside of the primary tumor for efficient metastasis. º Platelet-tumor cell contacts induce a mesenchymal-like metastatic phenotype º Platelet-derived TGF²1 is necessary but not sufficient for efficient metastasis º NF-ºB signaling is also necessary but not sufficient and synergizes with TGF² º Signals provided outside the primary tumor microenvironment promote metastasis
Cancer cell , résumé, 2010