Chou Sheng-Chieh, Chang Shu-Lun, Yu Cheng-Yeh, Lin Chao-I, Chang Yen-Ting, Chen Li-Fu, Li Jia-Yi, Pai Chen-Hsueh, Lin Shu-Rung, Cheng Wern-Cherng, Yuan Chang-Tsu, Lin Shu-Wha
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Thromb J. 2025 Apr 11;23(1):32. doi: 10.1186/s12959-025-00715-x.
Tissue factor (TF)-rich cancer microvesicles are correlated with thrombosis risk. Intrinsic coagulation factors are also associated with the risk of thrombosis in cancer patients. This study explored the roles of pancreatic cancer-derived microvesicles and intrinsic factors in thrombogenesis.
Human pancreatic cancer cell lines rich in TF (AsPC-1-TF, MIAPaCa-2-TF) or poor in TF [AsPC-1-TF(knockout) and MIAPaCa-2-TF] were generated for microvesicle preparation and injected into coagulation-defective mice. Inferior vena cava (IVC) clots and lung thrombosis were evaluated. Immunodeficient hemophilia A (NSG-HA) mice were orthotopically injected with the cells mentioned above, and the tumor and IVC clot weights were analyzed.
With the injection of TF microvesicles, IVC clots were rarely found in hemophilic mice. The TF and TF microvesicles resulted in few IVC clots in any mouse. Lung thrombosis was substantially reduced in the hemophilic mice infused with any microvesicle type. In orthotopic tumor models, TF cells grew faster than did TF cells. TF tumor-bearing NSG-WT mice had the most enormous IVC clots, whereas NSG-HA mice had no IVC clots.
Pancreatic cancer thrombosis induced by TF-expressing microvesicles strongly depended on FVIII and FIX, while VWF played a minor role. Moreover, TF, but not FVIII, was significantly related to tumor growth.
富含组织因子（TF）的癌症微泡与血栓形成风险相关。内源性凝血因子也与癌症患者的血栓形成风险有关。本研究探讨了胰腺癌来源的微泡和内源性因子在血栓形成中的作用。
构建富含TF的人胰腺癌细胞系（AsPC-1-TF、MIAPaCa-2-TF）或TF缺乏的细胞系[AsPC-1-TF（敲除）和MIAPaCa-2-TF]用于制备微泡，并将其注射到凝血缺陷小鼠体内。评估下腔静脉（IVC）血栓和肺血栓形成情况。将上述细胞原位注射到免疫缺陷的甲型血友病（NSG-HA）小鼠体内，分析肿瘤和IVC血栓重量。
注射TF微泡后，血友病小鼠中很少发现IVC血栓。TF和TF微泡在任何小鼠中均导致较少的IVC血栓。输注任何类型微泡的血友病小鼠肺血栓形成均显著减少。在原位肿瘤模型中，TF细胞比TF细胞生长更快。TF荷瘤NSG-WT小鼠的IVC血栓最大，而NSG-HA小鼠没有IVC血栓。
表达TF的微泡诱导的胰腺癌血栓形成强烈依赖于FVIII和FIX，而VWF起次要作用。此外，TF而非FVIII与肿瘤生长显著相关。
