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Updated: Aug 12, 2025
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Suppression of galectin-4 attenuates peritoneal metastasis of poorly differentiated gastric cancer cells
Hiroko Ideo1, Akiko Tsuchida2, Yoshio Takada2
1Laboratory of Glycobiology, The Noguchi Institute, 1-9-7, Kaga, Itabashi, Tokyo, 173-0003, Japan. ideo@noguchi.or.jp.
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.
Insights
Galectin-4 drives peritoneal metastasis in gastric cancer. Suppressing galectin-4 inhibits cancer cell spread and proliferation, highlighting its potential as a therapeutic target for this aggressive disease.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metastasis
Background:
- Peritoneal dissemination in gastric cancer is a severe, inoperable condition with limited treatment options.
- Novel therapeutic targets are urgently needed to combat metastatic and recurrent gastric cancer.
- Galectin-4 is specifically expressed in poorly differentiated gastric cancer cells prone to peritoneal spread.
Purpose of the Study:
- To investigate the role of galectin-4 in the peritoneal dissemination of gastric cancer.
- To evaluate galectin-4 as a potential diagnostic and therapeutic target.
Main Methods:
- Galectin-4 gene knockout in NUGC4 cells using CRISPR/Cas9.
- Assessment of cell proliferation and peritoneal metastasis in knockout, wild-type, and re-expressing cells.
- Western blotting, proximity ligation assays, siRNA knockdown, and immunohistochemistry to analyze galectin-4 expression and interactions.
Main Results:
- Suppression of galectin-4 significantly reduced gastric cancer cell proliferation and peritoneal metastasis.
- Galectin-4 knockout/knockdown decreased the expression of activated c-MET and CD44.
- Galectin-4 interacts with cell surface proteins CD44 and c-MET, mediated by its carbohydrate-binding ability.
- Galectin-4 was expressed in all examined patient samples with peritoneal metastatic gastric cancer.
Conclusions:
- Galectin-4 plays a crucial role in the peritoneal dissemination of poorly differentiated gastric cancer.
- Galectin-4 demonstrates significant potential as a diagnostic marker and therapeutic target for peritoneal gastric cancer metastasis.
