Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer.
نویسندگان
چکیده
Cancer patients often have an activated clotting system and are at increased risk for venous thrombosis. In the present study, we analyzed tissue factor (TF) expression in 4 different human pancreatic tumor cell lines for the purpose of producing derivative tumors in vivo. We found that 2 of the lines expressed TF and released TF-positive microparticles (MPs) into the culture medium. The majority of TF protein in the culture medium was associated with MPs. Only TF-positive cell lines activated coagulation in nude mice, and this activation was abolished by an anti-human TF Ab. Of the 2 TF-positive lines, only one produced detectable levels of human MP TF activity in the plasma when grown orthotopically in nude mice. Surprisingly, < 5% of human TF protein in plasma from tumor-bearing mice was associated with MPs. Mice with TF-positive tumors and elevated levels of circulating TF-positive MPs had increased thrombosis in a saphenous vein model. In contrast, we observed no difference in thrombus weight between tumor-bearing and control mice in an inferior vena cava stenosis model. The results of the present study using a xenograft mouse model suggest that tumor TF activates coagulation, whereas TF on circulating MPs may trigger venous thrombosis.
منابع مشابه
THROMBOSIS AND HEMOSTASIS Tumor-derived tissue factor activates coagulation and enhances thrombosis in a mouse xenograft model of human pancreatic cancer
1Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; 2Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; 3Department of Early Discovery Biochemistry, Genentech Inc, South San Francisco, CA; 4Division of Hematology/Oncology, Department of Internal Medicine, University of...
متن کاملTumorigenicity of Esophageal Cancer Stem Cells (ECSCs) in nude mouse xenograft model
Background and objectives: Modeling cancer in vivo is a very important tool to investigate cancer pathogenesis and molecular mechanisms involved in cancer progression. Laboratory mice are the most common animal used for rebuilding human cancer in vivo. Cancer stem cells (CSCs) are the main reason of failure in cancer therapy because of tumor relapse and metastasis. Isolation of cancer stem cell...
متن کاملTumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients.
Patients with cancer have an increased risk for venous thrombosis. Interestingly, different cancer types have different rates of thrombosis, with pancreatic cancer having one of the highest rates. However, the mechanisms responsible for the increase in venous thrombosis in patients with cancer are not understood. Tissue factor (TF) is a transmembrane receptor and primary initiator of blood coag...
متن کاملS100A4 promotes pancreatic cancer progression through a dual signaling pathway mediated by Src and focal adhesion kinase
S100A4 expression is associated with poor clinical outcomes of patients with pancreatic cancer. The effects of loss or gain of S100A4 were examined in pancreatic cancer cell lines. S100A4 downregulation remarkably reduces cell migration and invasion, inhibits proliferation, and induces apoptosis in pancreatic tumor cells. S100A4 downregulation results in significant cell growth inhibition and a...
متن کاملایجاد مدل زنوگرافت بومی تومور ویلمز در ایران و کاربردهای آن در توسعه مطالعات پیش بالینی
Background : Wilms' tumor (nephroblastoma) is the most common renal malignancy of childhood. This cancer is considered as an embryonal neoplasm that arises from nephrogenic blastemal. Despite advances in therapeutic success, survival rate is still not satisfactory in tumors with unfavorable histology and recurrent cases. On the other hand, late adverse effects of chemotherapy threaten the lif...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Blood
دوره 119 23 شماره
صفحات -
تاریخ انتشار 2012