腹膜播散是一种无法手术治疗且缺乏有效治疗方法的情况，主要出现在转移和/或复发性胃癌患者中。分子靶向药物的使用也受到限制，因此，寻找新的治疗靶点并加深我们对这种转移性癌症的理解是一个紧迫的需求。在这项研究中，我们关注了半乳糖凝集素-4，这种蛋白质专门表达在有高腹膜播散潜力的低分化细胞中。 我们利用CRISPR / Cas9介导的基因组编辑，在NUGC4细胞中敲除了半乳糖凝集素-4基因。将敲除细胞的增殖和腹膜癌形成与野生型和重新表达半乳糖凝集素-4的细胞进行比较。进行了蛋白质印迹和邻近连接检测，以识别受半乳糖凝集素-4表达影响的相关分子。使用特定的siRNA研究半乳糖凝集素-4沉默对细胞增殖和腹膜转移的影响。通过免疫组化检查10名胃癌患者的腹膜转移肿瘤中半乳糖凝集素-4的表达。 抑制半乳糖凝集素-4的表达降低了恶性胃癌细胞的增殖和腹膜转移。半乳糖凝集素-4敲除和沉默降低了激活的c-MET和CD44的表达。通过其糖结合能力，半乳糖凝集素-4被发现与细胞表面的几种蛋白质相互作用，包括CD44和c-MET。免疫组化显示所有被检查的患者的腹膜转移肿瘤细胞中都表达了半乳糖凝集素-4。 我们阐明了半乳糖凝集素-4在低分化胃癌细胞腹膜转移发展中的作用。我们的数据突出了半乳糖凝集素-4在胃癌腹膜转移诊断和治疗中的潜在作用。©2023年。作者在国际胃癌协会和日本胃癌协会的独家许可下发表。

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.