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@ARTICLE{Etemad:286085,
      author       = {M. Etemad and F. Christodoulou and S. Uhlig and J. C.
                      Hassel and P. Schrotz-King$^*$ and H. Brenner$^*$ and C. M.
                      Ulrich and K. Bieback and H. Klüter and P. Bugert},
      title        = {{C}-{T}ype {L}ectin-like {R}eceptor 2 {E}xpression {I}s
                      {D}ecreased upon {P}latelet {A}ctivation and {I}s {L}ower in
                      {M}ost {T}umor {E}ntities {C}ompared to {H}ealthy
                      {C}ontrols.},
      journal      = {Cancers},
      volume       = {15},
      number       = {23},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-02661},
      pages        = {5514},
      year         = {2023},
      abstract     = {The C-type lectin-like receptor 2 (CLEC-2) is expressed on
                      platelets and mediates binding to podoplanin (PDPN) on
                      various cell types. The binding to circulating tumor cells
                      (CTCs) leads to platelet activation and promotes metastatic
                      spread. An increased level of soluble CLEC-2 (sCLEC-2),
                      presumably released from activated platelets, was shown in
                      patients with thromboinflammatory and malignant disease.
                      However, the functional role of sCLEC-2 and the mechanism of
                      sCLEC-2 release are not known. In this study, we focused on
                      the effect of platelet activation on CLEC-2 expression and
                      the sCLEC-2 plasma level in patients with cancer. First,
                      citrated blood from healthy volunteer donors (n = 20) was
                      used to measure the effect of platelet stimulation by
                      classical agonists and PDPN on aggregation, CLEC-2
                      expression on platelets with flow cytometry, sCLEC-2 release
                      to the plasma with ELISA and total CLEC-2 expression with
                      Western blot analysis. Second, sCLEC-2 was determined in
                      plasma samples from healthy donors (285) and patients with
                      colorectal carcinoma (CRC; 194), melanoma (160), breast
                      cancer (BC; 99) or glioblastoma (49). PDPN caused a
                      significant increase in the aggregation response induced by
                      classical agonists. ADP or PDPN stimulation of platelets
                      caused a significant decrease in CLEC-2 on platelets and
                      sCLEC-2 in the plasma, whereas total CLEC-2 in platelet
                      lysates remained the same. Thus, the increased plasma level
                      of sCLEC-2 is not a suitable biomarker of platelet
                      activation. In patients with CRC (median 0.9 ng/mL),
                      melanoma (0.9 ng/mL) or BC (0.7 ng/mL), we found
                      significantly lower sCLEC-2 levels (p < 0.0001), whereas
                      patients with glioblastoma displayed higher levels (2.6
                      ng/mL; p = 0.0233) compared to healthy controls (2.1 ng/mL).
                      The low sCLEC-2 plasma level observed in most of the tumor
                      entities of our study presumably results from the
                      internalization of sCLEC-2 by activated platelets or binding
                      of sCLEC-2 to CTCs.},
      keywords     = {cancer thrombosis (Other) / platelet function (Other) /
                      podoplanin (Other) / soluble CLEC-2 (Other)},
      cin          = {C120 / C070},
      ddc          = {610},
      cid          = {I:(DE-He78)C120-20160331 / I:(DE-He78)C070-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38067218},
      pmc          = {pmc:PMC10705117},
      doi          = {10.3390/cancers15235514},
      url          = {https://inrepo02.dkfz.de/record/286085},
}