Inhibition of cancer cell‑platelet adhesion as a promising therapeutic target for preventing peritoneal dissemination of gastric cancer

Takashi Nakayama, Ryo Saito, Shinji Furuya, Katsutoshi Shoda, Suguru Maruyma, Koichi Takiguchi, Kensuke Shiraishi, Hidenori Akaike, Yoshihiko Kawaguchi, Hidetake Amemiya, Hiromichi Kawaida, Nagaharu Tsukiji, Toshiaki Shirai, Hideyuki Shinmori, Masami Yamamoto, Sachiyo Nomura, Tetsuya Tsukamoto, Katsue Suzuki-Inoue, Daisuke Ichikawa

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Platelets form complexes with gastric cancer (GC) cells via direct contact, enhancing their malignant behavior. In the present study, the molecules responsible for GC cell‑platelet interactions were examined and their therapeutic application in inhibiting the peritoneal dissemination of GC was investi‑ gated. First, the inhibitory effects of various candidate surface molecules were investigated on platelets and GC cells, such as C‑type lectin‑like receptor 2 (CLEC‑2), glycoprotein VI (GPVI) and integrin αIIbβ3, in the platelet‑induced enhancement of GC cell malignant potential. Second, the therapeutic effects of molecules responsible for the development and progres‑ sion of GC were investigated in a mouse model of peritoneal dissemination. Platelet‑induced enhancement of the migratory ability of GC cells was markedly inhibited by an anti‑GPVI antibody and inhibitor of galectin‑3, a GPVI ligand. However, neither the CLEC‑2 inhibitor nor the integrin‑blocking peptide significantly suppressed this enhanced migratory ability. In experiments using mouse GC cells and platelets, the migratory and invasive abilities enhanced by platelets were signifi‑ cantly suppressed by the anti‑GPVI antibody and galectin‑3 inhibitor. Furthermore, in vivo analyses demonstrated that the platelet‑induced enhancement of peritoneal dissemina‑ tion was significantly suppressed by the coadministration of anti‑GPVI antibody and galectin‑3 inhibitor, and was nearly eliminated by the combined treatment. The inhibition of adhesion resulting from GPVI‑galectin‑3 interaction may be a promising therapeutic strategy for preventing peritoneal dissemination in patients with GC.

Original languageEnglish
Article number538
JournalOncology Letters
Volume26
Issue number6
DOIs
Publication statusPublished - 12-2023

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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