Tissue factor over-expression by human pancreatic cancer cells BXPC3 is related to higher prothrombotic potential as compared to breast cancer cells MCF7

• Published in: Thrombosis research Vol. 129; no. 6; pp. 779 - 786
• Main Authors: Gerotziafas, Grigoris T, Galea, Vassiliki, Mbemba, Elisabeth, Khaterchi, Amir, Sassi, Mouna, Baccouche, Hela, Prengel, Claudie, van Dreden, Patrick, Hatmi, Mohamed, Bernaudin, Jean François, Elalamy, Ismail
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.06.2012; Elsevier
• Subjects: Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cardiology. Vascular system; Cell Line, Tumor; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Hematology, Oncology and Palliative Medicine; Humans; MCF-7 Cells; Medical sciences; pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Thrombin - genetics; Thrombin - metabolism; thrombin generation; Thromboplastin - biosynthesis; Thromboplastin - genetics; Thromboplastin - metabolism; tissue factor; venous thromboembolism; Venous Thromboembolism - genetics; Venous Thromboembolism - metabolism; Venous Thromboembolism - pathology; Vertebrates: cardiovascular system; breast cancer; pancreatic cancer; tissue factor; thrombin generation; venous thromboembolism; Breast disease; Tissue factor; Cardiovascular disease; Thrombin; Venous disease; Vascular disease; Pancreas cancer; Venous thrombosis; Thromboembolism; Tumor cell; Pancreatic disease; Human; Serine endopeptidases; Enzyme; Deep vein thrombosis; Breast cancer; Malignant tumor; Mammary gland diseases; Peptidases; Hydrolases; Digestive diseases; Cancer
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2011.07.049

Abstract Cancer histology influences the risk of venous thromboembolism and tissue factor (TF) is the key molecule in cancer-induced hypercoagulability. We investigated the relation between TF expression by pancreatic and breast cancer cells (BXPC3 and MCF7 respectively) and their capacity to trigger in vitro thrombin generation in normal human plasma. Flow cytometry and Western blot analysis for TF expression were performed using murine IgG1 monoclonal antibody against human TF. Real-time PCR for TFmRNA was also performed. Activity of TF expressed by cancer cells was measured with a specific chromogenic assay. Thrombin generation in PPP was assessed using calibrated automated thrombogram. Cancer cells were added to platelet poor plasma from healthy volunteers. In separate experiments cells were incubated with the anti-TF antibody at concentration that completely neutralized the activity of recombinant human TF on thrombin generation. BXPC3 cells expressed significantly higher amounts of functional TF as compared to MCF7 cells. Incubation of BXPC3 and MCF7 cells with PPP resulted in acceleration of the initiation phase of thrombin generation. BXPC3 cells manifested higher procoagulant potential than MCF7 cells. The incubation of BXPC3 or MCF7 cells with the anti-TF monoclonal antibody which resulted in reversal of their effect on thrombin generation. The present study establishes a link between the amount of TF expressed by cancer cells with their procoagulant activity. Both studied types of cancer cells trigger thrombin generation but they have different procoagulant potential. The procoagulant activity of BXPC3 and MCF7 cells is related to the amount of TF expressed. Kinetic parameters of thrombogram are the most relevant for the detection of the TF-dependent procoagulant activity of cancer cells. TF expression is one of the mechanisms by which cancer cells manifest their procoagulant potential but it is not the unique one. The present experimental model will allow the characterization the procoagulant fingerprint of cell lines from the same or different histological types of cancer.