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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Hiroko Ideo, Akiko Tsuchida, Yoshio Takada, Jun Kinoshita, Noriyuki Inaki, Toshinari Minamoto
• Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (Gastric Cancer) Vol. 26 Issue 3 Pg. 352-363 (05 2023) ISSN: 1436-3305 [Electronic] Japan
• PMID: 36695981 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.

Chemical References

• Galectin 4
• RNA, Small Interfering

Topics

• Humans
• Stomach Neoplasms (pathology)
• Peritoneal Neoplasms (secondary)
• Galectin 4 (genetics)
• Immunohistochemistry
• RNA, Small Interfering
• Cell Line, Tumor