PT - JOURNAL ARTICLE AU - Makoto Sano AU - Ryota Takahashi AU - Hideaki Ijichi AU - Kazunaga Ishigaki AU - Tomoharu Yamada AU - Koji Miyabayashi AU - Gen Kimura AU - Suguru Mizuno AU - Hiroyuki Kato AU - Hiroaki Fujiwara AU - Takuma Nakatsuka AU - Yasuo Tanaka AU - Jinsuk Kim AU - Yohei Masugi AU - Yasuyuki Morishita AU - Mariko Tanaka AU - Tetsuo Ushiku AU - Yousuke Nakai AU - Keisuke Tateishi AU - Yukimoto Ishii AU - Hiroyuki Isayama AU - Harold L Moses AU - Kazuhiko Koike TI - Blocking VCAM-1 inhibits pancreatic tumour progression and cancer-associated thrombosis/thromboembolism AID - 10.1136/gutjnl-2020-320608 DP - 2021 Sep 01 TA - Gut PG - 1713--1723 VI - 70 IP - 9 4099 - http://gut.bmj.com/content/70/9/1713.short 4100 - http://gut.bmj.com/content/70/9/1713.full SO - Gut2021 Sep 01; 70 AB - Objective Pancreatic ductal adenocarcinoma (PDAC) is the deadliest cancer. Cancer-associated thrombosis/thromboembolism (CAT), frequently observed in PDAC, is known as a poor prognostic factor. Here, we investigated the underlying mechanisms between PDAC and CAT, and performed a trial of therapeutic approach for PDAC using a genetically engineered mouse model, PKF (Ptf1acre/+;LSL-KrasG12D/+;Tgfbr2flox/flox ).Design Presence of CAT in PKF mice was detected by systemic autopsy. Plasma cytokines were screened by cytokine antibody array. Murine and human plasma atrial natriuretic peptide (ANP) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were determined by ELISA. Distribution of VCAM-1 in PKF mice and human autopsy samples was detected by immunohistochemistry. PKF mice were treated with anti-VCAM-1 antibody and the effects on survival, distribution of CAT and the tumour histology were analysed.Results We found spontaneous CAT with cardiomegaly in 68.4% PKF mice. Increase of plasma ANP and sVCAM-1 was observed in PKF mice and PDAC patients with CAT. VCAM-1 was detected in the activated endothelium and thrombi. Administration of anti-VCAM-1 antibody to PKF mice inhibited tumour growth, neutrophil/macrophage infiltration, tumour angiogenesis and progression of CAT; moreover, it dramatically extended survival (from 61 to 253 days, p<0.01).Conclusion Blocking VCAM-1/sVCAM-1 might be a potent therapeutic approach for PDAC as well as CAT, which can contribute to the prognosis. Increase of plasma ANP and sVCAM-1 might be a diagnostic approach for CAT in PDAC.All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to this study are included in the article and supplementary data.If you need to contact us, email address is:hideijichi-gi@umin.ac.jp.