We have developed an autochthonous and resectable model of intrahepatic cholangiocarcinoma which, after resection of the primary tumour, allows to study metastasis in the liver, lymph nodes, peritoneum, and the lungs. Transcriptome analysis of metastases revealed platelet activation signatures in liver, peritoneal, lymph node and lung metastasis but not in the primary tumour. Our data suggest crucial roles of platelets not only in metastasis formation but also metastasis progression and maintenance. Using genetic and biochemical tools, we will delineate the role of platelets in all steps of the metastatic cascade. Translational studies will explore the therapeutic potential of platelet-directed therapies, not only for metastasis suppression (adjuvant therapies), but also as part of combinatorial therapies for the treatment of advanced metastatic tumours.
