TY - JOUR
T1 - CXCR4-expressing Mist1+ progenitors in the gastric antrum contribute to gastric cancer development
AU - Sakitani, Kosuke
AU - Hayakawa, Yoku
AU - Deng, Huan
AU - Ariyama, Hiroshi
AU - Kinoshita, Hiroto
AU - Konishi, Mitsuru
AU - Ono, Satoshi
AU - Suzuki, Nobumi
AU - Ihara, Sozaburo
AU - Niu, Zhengchuan
AU - Kim, Woosook
AU - Tanaka, Takayuki
AU - Liu, Haibo
AU - Chen, Xiaowei
AU - Tailor, Yagnesh
AU - Fox, James G.
AU - Konieczny, Stephen F.
AU - Onodera, Hiroshi
AU - Sepulveda, Antonia R.
AU - Asfaha, Samuel
AU - Hirata, Yoshihiro
AU - Worthley, Daniel L.
AU - Koike, Kazuhiko
AU - Wang, Timothy C.
N1 - Funding Information:
of Health grants U54CA126513, R01CA093405, R01CA120979, R01DK052778, and by the Clyde Wu Family Foundation (T.C.W.), JSPS Research Fellowship for Young Scientists and Mitsukoshi health and Welfare Foundation (K.S.), the Project for Cancer Research And Therapeutic Evolution (P-CREATE) from the Japan Agency of Medical Research and Development, AMED, the KAKENHI Grant-in-Aid for Young Scientist Start-up and (A) (16H06749 and 17H05081), the Kobayashi Foundation for Cancer Research, the Mochida Memorial Foundation for Medical and Pharmacological Research, the Mitsubishi Foundation, Natural Sciences, the Advanced Research and Development Programs for Medical Innovation (PRIME) and the Tokyo Society of Medical Sciences (Y.H.), Foundation of Jiangxi Educational Committee (20151BAB215008, 20151BBG70200) (H.D.), and China Scholarship Council (Z.N.).
Funding Information:
This research was supported by National Institute
Publisher Copyright:
© Sakitani et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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U2 - 10.18632/oncotarget.22451
DO - 10.18632/oncotarget.22451
M3 - Article
AN - SCOPUS:85038431878
SN - 1949-2553
VL - 8
SP - 111012
EP - 111025
JO - Oncotarget
JF - Oncotarget
IS - 67
ER -
