Project Details
Abstract
The cancer cell metastasis including angiogenesis, migration, invasion, move to the
lymph and blood vessels, and translocation to anatomically distant organs, where after
extravasation they colonize the tissue to develop secondary metastases. Tumor cells can
stimulate platelet activation and form the aggregation complex with platelets in the vascular
circulation system. This interaction is termed as tumor cell-induced platelet aggregation
(TCIPA). The ability of tumor cells to induce platelet aggregation has been proven to highly
correlate with the metastatic capability of malignant tumor. Therefore, inhibiting TCIPA is
able to use as the strategies for treatment of tumor metastasis. Podoplanin (PDPN) is a
membrane protein found in many tumor cells, and correlates with their capacity to induce
platelet aggregation and to metastasise. Furthermore, PDPN also is a ligand of platelet C-type
lectin receptor (CLEC-2), and mediates activation of platelet. These indicate inhibiting the
interaction between CLEC-2 and PDPN is a therapy target for treatment of tumor metastasis.
A previous study enabled us to identify three components (LFH-7, LFH-20, and NB-1), which
selectively inhibited PDPN-induced platelet aggregation. Of these, NB-1 is a first small
molecular agent directly blocking interaction between CLEC-2 and PDPN. In addition, NB-1
is patent pending now. Therefore, the NB-1 and LFHs derivatives will be designed,
synthesized, evaluated, and developed using structural-based design. Finally, the
pharmacokinetic analysis of bioactive derivatives will also be determined herein.
Project IDs
Project ID:PC10401-0166
External Project ID:NSC102-2320-B182-008-MY3
External Project ID:NSC102-2320-B182-008-MY3
Status | Finished |
---|---|
Effective start/end date | 01/08/15 → 31/07/16 |
Keywords
- Tumor cell -induced platelet aggregation
- Podoplanin
- Metastasis
- Platelet C-type
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