Role of platelets in tumor growth and metastasis in ovarian cancer

• Applicant: Professorin Monika Hämmerle, Ph.D.
• Subject Area: Pathology
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 260791026

Thrombocytosis is a common condition associated with many types of solid neoplasms, including ovarian cancer. Pulmonary emboli and thrombosis are a major cause of death in cancer patients and overall survival as well as progression-free survival is reduced in patients with thrombocytosis compared to patients with normal platelet counts. Indeed, it is well accepted that platelets play crucial roles in tumor growth and metastasis as reduction of platelet number reduce tumor mass and progression. However, the exact mechanisms of infiltration and invasion into the tumor tissue as well as the surface markers needed for the interaction of platelets with cancer and endothelial cells are not well described so far. Moreover, it remains unknown if platelets show any structural differences upon interaction with different cell types or stimulation with various chemotherapeutics. Within this proposal two main aims will be carried out: Firstly, the mechanisms by which platelets infiltrate into the tumor tissue will be elucidated, as well as how the platelet infiltrate changes during different kinds of chemotherapy. Hereby, important surface receptors of platelets as well as cytokines secreted by the tumor or endothelial cells will be identified using whole genomics and proteomics techniques. Secondly, using different mouse models as well as in vitro assays, a systemic characterization of the interaction and communication between platelets and tumor or endothelial cells will be undertaken and its effect on tumor growth, cancer progression and metastasis as well as tumor angiogenesis will be analyzed with special respect to the non-coding RNA/miRNA content of platelet-derived microparticles and exosomes. It is crucial to resolve the underlying mechanisms and the impact of thrombocytosis in cancer which will likely identify novel biomarkers for tumor monitoring and predicting thromboembolic events and lead to the development of new strategies to block such effects.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Anil K. Sood