Koizumi Keiichi, Kato Shinichiro, Sakurai Hiroaki, Hashimoto Isaya, Yasumoto Kazuo, Saiki Ikuo
Division of Kampo Diagnostics, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
Front Biosci (Schol Ed). 2012 Jan 1;4(1):269-76. doi: 10.2741/s267.
Patients with advanced gastric carcinoma, especially peritoneal dissemination, have a poor prognosis. Various treatments have been used for peritoneal dissemination of gastric cancer, but there is no effective therapy for this condition. At present, similar proprieties of chemokines between trafficking of leukocytes during immune and inflammatory reactions and organ selective migration of cancer cells during metastasis are widely recognized. In particular, chemokine CXCL12 and its receptors CXCR4 are now known to play an important role in cancer progression. Recently, we reported for the first time that CXCR4 and its ligand, CXCL12, were involved in the development of peritoneal carcinomatosis of gastric cancer, and additionally, clarified the molecular mechanisms of the cell signaling pathways by which gastric cancer develops metastatic ability via CXCR4 and mTOR. In this review, we focus on the biological functions of chemokine receptors, particularly CXCR4 expressed on gastric cancer cells, and the therapeutic strategies targeting CXCR4-mediating signaling pathways in peritoneal carcinomatosis.
晚期胃癌患者，尤其是发生腹膜播散的患者，预后较差。针对胃癌腹膜播散已采用了多种治疗方法，但对于这种情况尚无有效的治疗手段。目前，免疫和炎症反应期间白细胞迁移与转移期间癌细胞器官选择性迁移过程中趋化因子的相似特性已得到广泛认可。特别是，趋化因子CXCL12及其受体CXCR4目前已知在癌症进展中起重要作用。最近，我们首次报道CXCR4及其配体CXCL12参与了胃癌腹膜转移瘤的发生发展，此外，还阐明了胃癌通过CXCR4和mTOR获得转移能力的细胞信号通路的分子机制。在本综述中，我们重点关注趋化因子受体的生物学功能，特别是胃癌细胞上表达的CXCR4，以及针对腹膜转移瘤中CXCR4介导的信号通路的治疗策略。
