Project Details
Abstract
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 IDs
Project ID:PC10507-0247
External Project ID:MOST105-2320-B182-029-MY3
External Project ID:MOST105-2320-B182-029-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/16 → 31/07/17 |
Keywords
- Podoplanin
- blood circulatory system
- cancer
- orthotopic animal model
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