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C-Type Lectin-like Receptor 2 Expression Is Decreased upon Platelet Activation and Is Lower in Most Tumor Entities
Mani Etemad1,2, Foteini Christodoulou1,2, Stefanie Uhlig3
1German Red Cross Blood Service Baden-Württemberg-Hessen, Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, 69117 Heidelberg, Germany.
Cancers
|December 9, 2023
Summary
Soluble C-type lectin-like receptor 2 (sCLEC-2) levels decrease upon platelet activation, indicating it is not a reliable biomarker for platelet activation in cancer. Most cancer patients showed lower sCLEC-2, except for glioblastoma.
Area of Science:
- Immunology
- Oncology
- Hematology
Background:
- C-type lectin-like receptor 2 (CLEC-2) on platelets binds podoplanin (PDPN) on tumor cells, promoting metastasis.
- Elevated soluble CLEC-2 (sCLEC-2) is observed in thromboinflammatory and malignant diseases, but its role and release mechanism are unclear.
Purpose of the Study:
- To investigate the effect of platelet activation on CLEC-2 expression and sCLEC-2 plasma levels in cancer patients.
- To determine if sCLEC-2 is a suitable biomarker for platelet activation in cancer.
Main Methods:
- Platelet stimulation with agonists and PDPN in healthy donors.
- Flow cytometry for CLEC-2 expression on platelets.
- ELISA for sCLEC-2 in plasma.
- Western blot for total CLEC-2 in platelet lysates.
- sCLEC-2 measurement in plasma from healthy controls and patients with colorectal carcinoma, melanoma, breast cancer, and glioblastoma.
Main Results:
- Platelet stimulation with ADP or PDPN decreased CLEC-2 on platelets and sCLEC-2 in plasma, while total CLEC-2 remained unchanged.
- sCLEC-2 is not a suitable biomarker for platelet activation.
- Significantly lower sCLEC-2 levels were found in patients with colorectal carcinoma, melanoma, and breast cancer compared to healthy controls.
- Glioblastoma patients showed significantly higher sCLEC-2 levels than healthy controls.
Conclusions:
- Increased plasma sCLEC-2 is not indicative of platelet activation.
- Low sCLEC-2 in most cancers may result from internalization by activated platelets or binding to circulating tumor cells (CTCs).
- Glioblastoma exhibits distinct sCLEC-2 regulation compared to other cancers studied.
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