Sakitani Kosuke, Hayakawa Yoku, Deng Huan, Ariyama Hiroshi, Kinoshita Hiroto, Konishi Mitsuru, Ono Satoshi, Suzuki Nobumi, Ihara Sozaburo, Niu Zhengchuan, Kim Woosook, Tanaka Takayuki, Liu Haibo, Chen Xiaowei, Tailor Yagnesh, Fox James G, Konieczny Stephen F, Onodera Hiroshi, Sepulveda Antonia R, Asfaha Samuel, Hirata Yoshihiro, Worthley Daniel L, Koike Kazuhiko, Wang Timothy C
Division of Digestive and Liver Disease, Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY, USA.
Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
Oncotarget. 2017 Nov 10;8(67):111012-111025. doi: 10.18632/oncotarget.22451. eCollection 2017 Dec 19.
was recently shown to identify a discrete population of stem cells within the isthmus of the oxyntic gland within the gastric corpus. Chief cells at the base of the gastric corpus also express . The relevance of expression as a marker of specific cell populations within the antral glands of the distal stomach, however, is unknown. Using -CreERT mice, we revealed that antral cells, distinct from the population in the corpus, comprise long-lived progenitors that reside within the antral isthmus above or CCK2R cells. antral progenitors can serve as an origin of antral tumors induced by loss of Apc or MNU treatment. antral progenitors, as well as other antral stem/progenitor population, express Cxcr4, and are located in close proximity to Cxcl12 (the Cxcr4 ligand)-expressing endothelium. During antral carcinogenesis, there is an expansion of Cxcr4 epithelial cells as well as the Cxcl12 perivascular niche. Deletion of Cxcl12 in endothelial cells or pharmacological blockade of Cxcr4 inhibits antral tumor growth. Cxcl12/Cxcr4 signaling may be a potential therapeutic target.
最近的研究表明，在胃体部胃底腺峡部内可识别出一群离散的干细胞。胃体部底部的主细胞也表达 。然而， 表达作为远端胃窦腺内特定细胞群体标志物的相关性尚不清楚。利用 -CreERT 小鼠，我们发现胃窦细胞不同于胃体部的 群体，包含位于 或 CCK2R 细胞上方胃窦峡部的长寿命祖细胞。胃窦祖细胞可作为由 Apc 缺失或 MNU 处理诱导的胃窦肿瘤的起源。胃窦祖细胞以及其他胃窦干/祖细胞群体表达 Cxcr4，并位于表达 Cxcl12（Cxcr4 配体）的内皮细胞附近。在胃窦癌发生过程中，Cxcr4 上皮细胞以及 Cxcl12 血管周围微环境会发生扩张。内皮细胞中 Cxcl12 的缺失或 Cxcr4 的药理学阻断可抑制胃窦肿瘤生长。Cxcl12/Cxcr4 信号通路可能是一个潜在的治疗靶点。
