Suppression of galectin-4 attenuates peritoneal metastasis of poorly differentiated gastric cancer cells.

Hiroko Ideo, Akiko Tsuchida, Yoshio Takada, Jun Kinoshita, Noriyuki Inaki, Toshinari Minamoto

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2023 May

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Peritoneal dissemination, most often seen in metastatic and/or recurrent gastric cancer, is an inoperable condition that lacks effective treatment. The use of molecular targeted drugs is also limited; therefore, identifying novel therapeutic targets and improving our understanding of this metastatic cancer are an urgent requirement. In this study, we focused on galectin-4, which is specifically expressed in poorly differentiated cells with high potential for peritoneal dissemination. We knocked out the galectin-4 gene in NUGC4 cells using CRISPR/Cas9-mediated genome editing. Proliferation and peritoneal cancer formation in knockout cells were compared with those in wild-type and galectin-4 re-expressing cells. Western blotting and proximity ligation assays were performed to identify associated molecules affected by the expression of galectin-4. The effect of galectin-4 knockdown on cell proliferation and peritoneal metastasis was studied using a specific siRNA. Expression of galectin-4 in peritoneal metastatic tumors from 10 patients with gastric cancer was examined by immunohistochemistry. Suppression of galectin-4 expression reduced proliferation and peritoneal metastasis of malignant gastric cancer cells. Galectin-4 knockout and knockdown reduced the expression of activated c-MET and CD44. Galectin-4 was found to interact with several proteins on the cell surface, including CD44 and c-MET, via its carbohydrate-binding ability. Immunohistochemistry showed galectin-4 expression in peritoneal metastatic tumor cells in all patients examined. We clarified the role of galectin-4 in the development of peritoneal dissemination of poorly differentiated gastric cancer cells. Our data highlight the diagnostic and therapeutic potential of galectin-4 in the peritoneal dissemination of gastric cancer. © 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.

Citation

Hiroko Ideo, Akiko Tsuchida, Yoshio Takada, Jun Kinoshita, Noriyuki Inaki, Toshinari Minamoto. Suppression of galectin-4 attenuates peritoneal metastasis of poorly differentiated gastric cancer cells. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2023 May;26(3):352-363