Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

The Role of Platelets in Cancer: An exploration of the nature of the cytokine secretion profile in during cancer progression

Niamh Moran, Molecular & Cellular Therapeutics. Keywords: cancer, cardiovascular disorders, platelet, metastasis

Platelet activation in normal individuals is accompanied by thrombus development and a parallel secretion of bioactive proteins from platelet granules, including inflammatory factors, growth factors, chemokines and cytokines . The precise content of the secretome varies depending on the the physiological or pathological stimulus (Battinelli et al. 2011).
We recently demonstrated that isolated cancer cells can induce platelet aggregation and thrombus formation. Metastatic tumour cell lines do this more efficiently than non-metastatic cell lines (Mitrugno et al. 2014). Platelet secretion is also enhanced by cancer cells in a manner related to their metastatic capacity. Moreover, platelets appear to have an ability to sequester pro-cancer cytokines, secreted by the metastatic progenitor cells ( Kerr et al, 2010). However, no systemmatic assessment of the cancer-induced platelet secretome has been undertaken to date. It is our hypothesis that the bioactive agents released in the platelet secretome during cancer may serve to functionally affect / facilitate vascular changes and metastatic angiogeniesis during cancer.
In this proposal we will characterize the nature of the platelet secretome using a Multiplex ELISA platform to quantitatively detect human inflammatory growth factors, chemokines and cytokines. We will compare the platelet secretome of normal healthy donors with secretomes from patient groups with staged cancer diagnosis. In parallel, we will examine the changes in platelet secretomes in a mouse model of cancer metastasis .

Battinelli EM, Markens BA, Kulenthirarajan RA, Machlus KR, Flaumenhaft R, Italiano JE Jr.Anticoagulation inhibits tumor cell-mediated release of platelet angiogenic proteins and diminishesplatelet angiogenic response. Blood. 2014 Jan 2;123(1):101-12. PMID:24065244
Mitrugno A, Williams D, Kerrigan SW, Moran N. A novel and essential role for FcγRIIa in cancer cell-induced platelet activation Blood. 2014 Jan 9;123(2):249-60.
Kerr BA, Miocinovic R, Smith AK, Klein EA, Byzova TV.Comparison of tumor and microenvironment secretomes in plasma and in platelets during prostate cancer growth in a xenograft model. Neoplasia. 2010 May;12(5):388-96.

Mentors Niamh Moran. nmoran@rcsi.ie, (01) 4022153.