Direct Signaling Between Platelets and Cancer Cells Induces an Epithelial-Mesenchymal-Like Transition and Promotes Metastasis

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 show that transient platelet-tumor cell interactions are sufficient to prime tumor cells for subsequent metastasis. Platelet-derived TGF-beta and direct platelet-tumor cell contacts synergistically activate the TGF-beta/Smad and NF-kappaB pathways in cancer cells, resulting in their transition to an invasive mesenchymal-like phenotype and enhanced metastasis in vivo. Inhibition of NF-kappaB signaling in cancer cells or ablation of TGF-beta1 expression solely in platelets protects against lung metastasis in vivo. Thus

ORGANISM(S): Mus musculus

SUBMITTER: Charles Whittaker 

PROVIDER: E-GEOD-27456 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress