Synopsis of platelet surface receptors and their putative roles in hematogenous tumor metastasis
| Platelet receptor . | Proposed implication in metastasis . |
|---|---|
| GPIb-IX-V | Questionable importance for TCIPA, mechanism unclear |
| GPIbα knockout mice show reduced metastasis | |
| Blockade of GPIbα with monovalent, monoclonal antibodies (Fab fragments) leads to enhanced metastasis | |
| GPVI | Hitherto, no association to metastasis or TCIPA |
| Integrin αIIbβ3 (GPIIb/IIIa) | Mediation of TCIPA |
| Platelet αIIbβ3 essential for pulmonary metastasis in various mouse models and a variety of cancer cell lines | |
| Aberrant expression on various tumor cell lines, enhancing their malignant potential | |
| Regulation of the release of angiogenic factors (vascular endothelial growth factor) from platelet granules upon tumor cell-induced platelet activation | |
| Integrin α2β1 (VLA-2) | Expressed by some tumor cells to facilitate binding to the ECM |
| ADP receptors | Release of ADP from platelet granules upon platelet activation, leading to secondary enhancement of TCIPA |
| Capability of some tumor cells to produce and release ADP themselves | |
| P-selectin | Binding of sialylated fucosylated glycans on mucin and nonmucin structures on cancer cell lines |
| Mediation of cancer cell interactions with activated platelets | |
| Enabling of tumor cell rolling on endothelial cells through endothelial P-selectin | |
| Thrombin receptors (PARs) | Enhancement of tumor cell-platelet interactions by activation of platelet or tumor cell PARs |
| Enhancement of tumor cell-endothelial cell interactions through thrombin | |
| Stimulation of integrin signaling in tumor cells | |
| Increase of metastatic foci in vivo through thrombin application, reduction of metastasis in PAR-4–deficient mice |
| Platelet receptor . | Proposed implication in metastasis . |
|---|---|
| GPIb-IX-V | Questionable importance for TCIPA, mechanism unclear |
| GPIbα knockout mice show reduced metastasis | |
| Blockade of GPIbα with monovalent, monoclonal antibodies (Fab fragments) leads to enhanced metastasis | |
| GPVI | Hitherto, no association to metastasis or TCIPA |
| Integrin αIIbβ3 (GPIIb/IIIa) | Mediation of TCIPA |
| Platelet αIIbβ3 essential for pulmonary metastasis in various mouse models and a variety of cancer cell lines | |
| Aberrant expression on various tumor cell lines, enhancing their malignant potential | |
| Regulation of the release of angiogenic factors (vascular endothelial growth factor) from platelet granules upon tumor cell-induced platelet activation | |
| Integrin α2β1 (VLA-2) | Expressed by some tumor cells to facilitate binding to the ECM |
| ADP receptors | Release of ADP from platelet granules upon platelet activation, leading to secondary enhancement of TCIPA |
| Capability of some tumor cells to produce and release ADP themselves | |
| P-selectin | Binding of sialylated fucosylated glycans on mucin and nonmucin structures on cancer cell lines |
| Mediation of cancer cell interactions with activated platelets | |
| Enabling of tumor cell rolling on endothelial cells through endothelial P-selectin | |
| Thrombin receptors (PARs) | Enhancement of tumor cell-platelet interactions by activation of platelet or tumor cell PARs |
| Enhancement of tumor cell-endothelial cell interactions through thrombin | |
| Stimulation of integrin signaling in tumor cells | |
| Increase of metastatic foci in vivo through thrombin application, reduction of metastasis in PAR-4–deficient mice |
TCIPA indicates tumor cell-induced platelet aggregation; ECM, extracellular matrix; ADP, adenosine diphosphate; and PARs, protease-activated receptors.