title: 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 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 TGFβ and direct platelet-tumor cell contacts synergistically activate the TGFβ/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 TGFβ1 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.
authors.affiliation: Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labelle
authors.forename: Shahinoor
authors.initials: S
authors.lastname: Begum
authors.forename: Richard O
authors.initials: RO
authors.lastname: Hynes
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D053773:Transforming Growth Factor beta1
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