CXCR4-expressing Mist1+ progenitors in the gastric antrum contribute to gastric cancer development
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oncotarget-08-111012.pdf
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13.78 MB
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Author(s)
Sakitani, Kosuke
Hayakawa, Yoku
Deng, Huan
Ariyama, Hiroshi
Kinoshita, Hiroto
Konishi, Mitsuru
Ono, Satoshi
Suzuki, Nobumi
Ihara, Sozaburo
Niu, Zhengchuan
Date Issued
November 2017
Journal
Oncotarget
Publisher
Impact Journals, LLC
Citation
Sakitani, Kosuke, Yoku Hayakawa, Huan Deng, Hiroshi Ariyama, Hiroto Kinoshita, Mitsuru Konishi, Satoshi Ono, et al. “CXCR4-Expressing Mist1+ Progenitors in the Gastric Antrum Contribute to Gastric Cancer Development.” Oncotarget 8, no. 67 (November 15, 2017).
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 3.0 Unported license
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DOI of Published Version
https://doi.org/10.18632/ONCOTARGET.22451
