PB0941 - Pancreatic cancer cells and derived microvesicles induce thrombosis in coagulation factor deficient mouse models

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Sheng-Chieh Chou, MD. (he/him/his)

Hematologist
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital
Taipei, Taipei, Taiwan (Republic of China)

Co-Author(s)

SC

Shu-Lun Chang

Research assistant
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University
Taipei, Taipei, Taiwan (Republic of China)
CY

Cheng-Yeh Yu

Master student
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University
Taipei, Taipei, Taiwan (Republic of China)
CL

Chao-I Lin

Master student
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University
Taipei, Taipei, Taiwan (Republic of China)
JL

Jia-Yi Li

Research assistant
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University
Taipei, Taipei, Taiwan (Republic of China)
CP

Chen‑Hsueh Pai

PostDoctorial fellow
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University
Taipei, Taipei, Taiwan (Republic of China)
SL

Shu-Rung Lin

Associate professor
Department of Bioscience Technology, College of Science, Chung-Yuan Christian University
Taoyuan, Taoyuan, Taiwan (Republic of China)
WC

Wern-Cherng Cheng

Pathologist
Department of Laboratory Medicine, National Taiwan University Hospital
Taipei, Taipei, Taiwan (Republic of China)
SL

Shu-Wha Lin

Professor
Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University; Department of Laboratory Medicine, National Taiwan University Hospital
Taipei, Taipei, Taiwan (Republic of China)

Background: Pancreatic cancer is the most thrombogenic cancer and the mechanism for which has not been fully elucidated.

Aims: To explore the role of intrinsic pathway in thrombogenesis of pancreatic cancer, we use human pancreatic cancer cell lines and their microvesicles for thrombogenic studies in gene knockout mice.

Methods: Human pancreatic cancer cell lines, AsPC-1, with tissue factor (TF) expression, MIAPaCa-2, without TF expression, CRISPR/Cas9-created TF-knockout AsPC-1(TFKO), and TF-overexpressed MIAPaCa-2(TFexp) were used. Hemophilia A (HA), Hemophilia B (HB) mice were of C57BL/6J origin. These cells were orthotopically transplanted into pancreas of immunodeficient (NSG) and immunodeficient hemophilia A (NSG/HA) mice. Thrombin-antithrombin complex (TAT), d-dimer and tumor growth were evaluated. Microvesicles isolated from cell line cultures were equally injected into HA, HB and wild type (WT) mice, followed by performing inferior vena cava (IVC) stenosis. Thrombi in IVC and lung vessels were evaluated.

Results: TF-positive cells grew better than TF-negative ones in HA/NSG mice but they grew similarly in NSG mice. TAT and d-dimer were higher in NSG mice transplanted with TF-positive than those with TF-negative cells. These differences were not present in HA/NSG mice. With infusion of TF-positive microvesicles, thrombi within IVC and lung vessels were significantly reduced in HA or HB mice compared to WT mice. With infusion of TF-negative microvesicles, all mice had nearly no thrombus formation within IVC, but there were still significantly more pulmonary thrombi in WT mice than in HA or HB mice.

Conclusion(s): Intrinsic coagulation may promote the proliferation of TF negative-pancreatic cancer cells in a mouse orthotopic transplantation model. TF-positive tumors have higher thrombogenesis potential in normal but attenuated in intrinsic-pathway deficient condition. Factor VIII and IX may play a role in thrombosis of pancreatic cancer.