CXCR4-expressing Mist1+ progenitors in the gastric antrum contribute to gastric cancer development
| Autor: | Timothy C. Wang, James G. Fox, Sozaburo Ihara, Mitsuru Konishi, Yagnesh Tailor, Takayuki Tanaka, Yoshihiro Hirata, Kazuhiko Koike, Xiaowei Chen, Hiroshi Onodera, Woosook Kim, Daniel L. Worthley, Hiroto Kinoshita, Antonia R. Sepulveda, Kosuke Sakitani, Haibo Liu, Stephen F. Konieczny, Samuel Asfaha, Zhengchuan Niu, Hiroshi Ariyama, Satoshi Ono, Nobumi Suzuki, Yoku Hayakawa, Huan Deng |
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| Přispěvatelé: | Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Liu, Haibo, Fox, James G, Wang, Tim |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system Population Biology medicine.disease_cause CXCR4 digestive system 03 medical and health sciences Cxcr4 medicine Mist1 cxcl12 Progenitor cell education Antrum Cxcl12 education.field_of_study Stem cell gastric cancer digestive oral and skin physiology LGR5 digestive system diseases 3. Good health Gastric chief cell stem cell 030104 developmental biology Oncology mist1 Cancer research Carcinogenesis Gastric cancer cxcr4 Research Paper |
| Zdroj: | Oncotarget Paediatrics Publications |
| ISSN: | 1949-2553 |
| Popis: | Mist1 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 Mist1. The relevance of Mist1 expression as a marker of specific cell populations within the antral glands of the distal stomach, however, is unknown. Using Mist1-CreERT mice, we revealed that Mist1+ antral cells, distinct from the Mist1+population in the corpus, comprise long-lived progenitors that reside within the antral isthmus above Lgr5+or CCK2R+cells. Mist1+ antral progenitors can serve as an origin of antral tumors induced by loss of Apc or MNU treatment. Mist1+ 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. National Institute of Health (U.S.) (grant U54CA126513) National Institute of Health (U.S.) (grant R01CA093405) National Institute of Health (U.S.) (grant R01CA120979) National Institute of Health (U.S.) (grant R01DK052778) Clyde Wu Family Foundation |
| Databáze: | OpenAIRE |
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