The Interplays between Cancer Cells with Podoplanin Expression and the Blood Circulatory System

The molecules that are closely associated with haemostasis and thrombosis play a pivotal role in cancer progression and metastasis. Podoplanin (PDPN) is a membranous sialoglycoprotein that binds to platelet surface receptor CLEC-2 and aggregates platelets with no relation to plasma components. PDPN expression has been shown to involve in cancer progression of several cancer types. In particular, a number of studies demonstrated the prognostic value of PDPN for the patients with oral squamous cell carcinoma (OSCC). OSCC is thereby a suitable type of cancer to unveil the functional impacts of PDPN in cancer progression. However, the molecular basis for the involvement of PDPN in caner progression is still largely unknown. Recently, we have established an orthotopic animal model that allows in vivo growth of OSCC cells “in situ”. Our preliminary studies further revealed that PDPN expression does not alter the tumor growth but is a poor prognostic factor of animal survival, consistent with the findings in clinical studies. In this grant proposal, we will investigate whether PDPN-expressing cancer cells interacts with the blood cells in the circulatory system and infiltrated into the primary organ site and whether the interaction is crucial to the pathophysiological function of PDPN, thereby explaining PDPN a poor prognostic factor in cancer progression. In the first and second year, orthotopic mouse model will be used to confirm the functional impacts of PDPN expression on animal survival and in vivo growth of OSCC cells. In the second and third year, we will focus on elucidating the molecular basis for PDPN acting as a poor prognostic factor in cancer progression of OSCC cells. In the third year, we will investigate whether blockage of endogenous PDPN receptor CLEC-2 activation is effective in interfering PDPN-mediated cancer progression of OSCC cells. The accomplishment of this grant proposal will contribute to understanding the pathophysiological function of PDPN in cancer. This information obtained from this study should provide insight whether PDPN is an idea biomarker and molecular target for development of therapeutic approaches in the treatment of patients with OSCC.

Project ID:PC10701-0284
External Project ID:MOST105-2320-B182-029-MY3