PMID- 30335544 OWN - NLM STAT- MEDLINE DCOM- 20181219 LR - 20181219 IS - 1369-1635 (Electronic) IS - 0953-7104 (Linking) VI - 29 IP - 8 DP - 2018 Dec TI - Sushi Domain Containing 2 (SUSD2) inhibits platelet activation and binding to high-grade serous ovarian carcinoma cells. PG - 834-837 LID - 10.1080/09537104.2018.1530345 [doi] AB - Platelets play a central role in primary hemostasis affecting tumor survival and metastases. Tumors induce platelets to aggregate and bind to the cancer cells, resulting in protection from immune surveillance and often leading to thrombocytosis. In ovarian cancer (OvCa), one-third of patients present with thrombocytosis, a diagnosis that correlates with shorter survival. SUSD2 (SUShi Domain containing 2), a type I transmembrane protein, shown to inhibit metastatic processes in high-grade serous ovarian carcinoma (HGSOC), is expressed on endothelial cells and thus may influence platelet reactivity. As such, we hypothesized that SUSD2 levels in ovarian cancer-derived cell lines influence platelet activation. We incubated OvCa non-targeting (NT) and SUSD2 knockdown (KD) cell lines with labeled platelets and quantified platelet binding, as well as GPIIb/IIIa integrin activation. The role of GPIIb/IIIa in tumor cell/platelet interaction was also examined by measuring cell-cell adhesion in the presence of eptifibatide. We found that platelets exposed to OvCa cells with low SUSD2 expression display increased tumor cell-platelet binding along with an increase in GPIIb/IIIa receptor activation. As such, platelet activation and binding to HGSOC cells was inversely correlated with the presence of SUSD2. This represents one of the first tumor proteins known to provide differential platelet interaction based on protein status. FAU - Lager, Tyson W AU - Lager TW AD - a Department of Biology , Augustana University , Sioux Falls , SD , USA. FAU - Roetman, Jessica J AU - Roetman JJ AD - a Department of Biology , Augustana University , Sioux Falls , SD , USA. FAU - Kunkel, Jacob AU - Kunkel J AD - a Department of Biology , Augustana University , Sioux Falls , SD , USA. FAU - Thacker, Megan AU - Thacker M AD - a Department of Biology , Augustana University , Sioux Falls , SD , USA. FAU - Sheets, Jordan N AU - Sheets JN AD - b Cancer Biology Research Center, Sanford Research , Sanford School of Medicine of the University of South Dakota , Sioux Falls , SD , USA. FAU - Egland, Kristi A AU - Egland KA AD - b Cancer Biology Research Center, Sanford Research , Sanford School of Medicine of the University of South Dakota , Sioux Falls , SD , USA. FAU - Miles, Cecelia M AU - Miles CM AD - a Department of Biology , Augustana University , Sioux Falls , SD , USA. FAU - Larson, Mark K AU - Larson MK AD - a Department of Biology , Augustana University , Sioux Falls , SD , USA. FAU - Gubbels, Jennifer A A AU - Gubbels JAA AUID- ORCID: 0000-0001-9878-0065 AD - a Department of Biology , Augustana University , Sioux Falls , SD , USA. LA - eng PT - Journal Article DEP - 20181018 PL - England TA - Platelets JT - Platelets JID - 9208117 RN - 0 (Membrane Glycoproteins) RN - 0 (Neoplasm Proteins) RN - 0 (SUSD2 protein, human) SB - IM MH - Blood Platelets/*metabolism/pathology MH - Cell Adhesion MH - Cell Line, Tumor MH - Coculture Techniques MH - Female MH - Humans MH - Membrane Glycoproteins/*metabolism MH - Neoplasm Proteins/*metabolism MH - Ovarian Neoplasms/*metabolism/pathology MH - *Platelet Activation OTO - NOTNLM OT - GPIIb/IIIa OT - SUSD2 OT - ovarian cancer EDAT- 2018/10/20 06:00 MHDA- 2018/12/20 06:00 CRDT- 2018/10/19 06:00 PHST- 2018/10/20 06:00 [pubmed] PHST- 2018/12/20 06:00 [medline] PHST- 2018/10/19 06:00 [entrez] AID - 10.1080/09537104.2018.1530345 [doi] PST - ppublish SO - Platelets. 2018 Dec;29(8):834-837. doi: 10.1080/09537104.2018.1530345. Epub 2018 Oct 18.