RT Journal Article
SR Electronic
T1 Blocking VCAM-1 inhibits pancreatic tumour progression and cancer-associated thrombosis/thromboembolism
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1713
OP 1723
DO 10.1136/gutjnl-2020-320608
VO 70
IS 9
A1 Sano, Makoto
A1 Takahashi, Ryota
A1 Ijichi, Hideaki
A1 Ishigaki, Kazunaga
A1 Yamada, Tomoharu
A1 Miyabayashi, Koji
A1 Kimura, Gen
A1 Mizuno, Suguru
A1 Kato, Hiroyuki
A1 Fujiwara, Hiroaki
A1 Nakatsuka, Takuma
A1 Tanaka, Yasuo
A1 Kim, Jinsuk
A1 Masugi, Yohei
A1 Morishita, Yasuyuki
A1 Tanaka, Mariko
A1 Ushiku, Tetsuo
A1 Nakai, Yousuke
A1 Tateishi, Keisuke
A1 Ishii, Yukimoto
A1 Isayama, Hiroyuki
A1 Moses, Harold L
A1 Koike, Kazuhiko
YR 2021
UL http://gut.bmj.com/content/70/9/1713.abstract
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.