Xia Wang1, Biao Liu1, Mengqiao Xu2, Yizhi Jiang3, Jundong Zhou1, Jun Yang1, Haidi Gu1, Changgeng Ruan2, Jinchang Wu4, Yiming Zhao5. 1. The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215006, Jiangsu, China. 2. Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of the Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, Jiangsu, China. 3. Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of the Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China. 4. The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 215006, Jiangsu, China; The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu, China. Electronic address: wjinchang@sina.com. 5. Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of the Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China; Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, Jiangsu, China. Electronic address: zhaoyimingbox@163.com.
Abstract
BACKGROUND: Patients with cancer are at a high risk of venous thromboembolism (VTE), studies have shown that high expression of podoplanin (PDPN) in tumors is associated with increased risk of VTE. METHODS: Two human malignant cell lines (NCI-H226 and C8161) expressing high levels of PDPN were selected to explore the role of platelet in cancer-associated venous thrombosis in vitro and in vivo. Immunohistochemical staining using anti-PDPN antibody was performed in the pulmonary carcinoma patients. RESULTS: Both NCI-H226 and C8161 cells expressing high PDPN triggered platelet activation via CLEC-2 in vitro, which was abrogated by an anti-PDPN antibody SZ-168. Furthermore, the in vivo study revealed that injection of CHO-PDPN or C8161 in two mouse model of venous thrombosis activated platelets, increased platelet counts and enhanced thrombosis. More importantly, PDPN-enhanced thrombosis was reduced in mice treated with SZ168. A total of 63.3% tumor specimens stained positive for PDPN. High PDPN expression was associated with an increased risk of VTE and poor prognosis. CONCLUSIONS: PDPN expression in tumors induced platelet activation and was related to a high risk of VTE via platelet activation. SZ168 inhibited PDPN-induced platelet activation in vitro and decreased the incidence of VTE in mice.
BACKGROUND:Patients with cancer are at a high risk of venous thromboembolism (VTE), studies have shown that high expression of podoplanin (PDPN) in tumors is associated with increased risk of VTE. METHODS: Two human malignant cell lines (NCI-H226 and C8161) expressing high levels of PDPN were selected to explore the role of platelet in cancer-associated venous thrombosis in vitro and in vivo. Immunohistochemical staining using anti-PDPN antibody was performed in the pulmonary carcinomapatients. RESULTS: Both NCI-H226 and C8161 cells expressing high PDPN triggered platelet activation via CLEC-2 in vitro, which was abrogated by an anti-PDPN antibody SZ-168. Furthermore, the in vivo study revealed that injection of CHO-PDPN or C8161 in two mouse model of venous thrombosis activated platelets, increased platelet counts and enhanced thrombosis. More importantly, PDPN-enhanced thrombosis was reduced in mice treated with SZ168. A total of 63.3% tumor specimens stained positive for PDPN. High PDPN expression was associated with an increased risk of VTE and poor prognosis. CONCLUSIONS:PDPN expression in tumors induced platelet activation and was related to a high risk of VTE via platelet activation. SZ168 inhibited PDPN-induced platelet activation in vitro and decreased the incidence of VTE in mice.
Authors: Fleur H J Kaptein; Milou A M Stals; Maaike Y Kapteijn; Suzanne C Cannegieter; Linda Dirven; Sjoerd G van Duinen; Ronald van Eijk; Menno V Huisman; Eva E Klaase; Martin J B Taphoorn; Henri H Versteeg; Jeroen T Buijs; Johan A F Koekkoek; Frederikus A Klok Journal: J Thromb Haemost Date: 2022-05-09 Impact factor: 16.036