PB1418 - Mucin 1 and venous thrombosis in tumor-bearing mice and patients with cancer

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Yohei Hisada, PhD

Assistant Professor
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States

Co-Author(s)

Tomohiro Kawano, MD, PhD

Assistant Professor
Department of Neurology, University of Osaka
Suita, Osaka, Japan
Cornelia Englisch, MD

PhD Student
Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna
Vienna, Wien, Austria
DP

David Paul

Assistant Professor
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Ingrid Pabinger

Professor
Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna
Vienna, Wien, Austria
Cihan Ay, MD

Professor
Division of Hematology and Hemostaseology, Department of Medicine I, Medical University of Vienna
Vienna, Wien, Austria
Nigel Mackman, PhD

Professor
Univerisity of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States

Background: Transmembrane mucins are overexpressed in a variety of human malignancies. Mucin-1 (MUC-1) is overexpressed in breast, lung, pancreatic, ovarian and prostate cancer. Injection of a mucin preparation from a human colonic adenocarcinoma into mice induced the formation of platelet-rich microthrombi suggesting that mucins play a role in cancer-associated thrombosis.

Aims: To determine the role of MUC-1 and venous thrombosis in a mouse model and patients with cancer.

Methods: A mouse tumor model was used with human tumors expressing high levels of MUC-1 (HPAF-II) grown in the pancreas of Crl:NU-Foxn1nu male mice. Levels of MUC-1 in the plasma were measured using an enzyme-linked immunosorbent assay (ELISA). Venous thrombosis was induced in mice with the inferior vena cava stasis model. MUC-1 in venous thrombi from tumor-bearing mice was assessed by western blotting. In a nested case-control study, MUC-1 was measured in plasma from patients with stomach (n = 15), colorectal (n = 21) or pancreatic (n =22) cancer with (n = 20) or without (n = 38) venous thromboembolism (VTE) by ELISA (Table 1).

Results: Circulating MUC-1 was present in the plasma of mice bearing high MUC-1 expressing tumors. HPAF-II tumor-bearing mice had increased weight of venous thrombi compared to mice without tumors (Figure 1, mean ± standard deviation: 29.58 ± 7.02 vs 20.00 ± 3.67 mg, P < 0.05). MUC-1 was present in venous thrombi from mice bearing HPAF-II tumors. While patients with stomach or pancreatic cancer and VTE showed a trend toward a significantly higher level of MUC-1 compared to patients without VTE (median [interquartile range]: 16,140 [12,705-20,545] vs 12,734 [10,031-16,123] mU/mL, P = 0.08), this was not observed in patients with colorectal cancer (median [interquartile range]: 10,570 [7,145-12,995] vs 14,260 [7,951-17,450] mU/mL, P = 0.322).

Conclusion(s): Further studies are needed to determine the association between MUC-1 and VTE in patients with cancer.