Chemokine 25–induced signaling suppresses colon cancer invasion and metastasis
作者： Huanhuan Joyce Chen , Robert Edwards , Serena Tucci , Pengcheng Bu , Jeff Milsom
DOI: 10.1172/JCI62110
关键词: Cancer research 、 Notch signaling pathway 、 Biology 、 Chemokine 、 Colorectal cancer 、 Metastasis 、 CCL25 、 Primary tumor 、 Chemokine receptor 、 CCR9
摘要: Chemotactic cytokines (chemokines) can help regulate tumor cell invasion and metastasis. Here, we show that chemokine 25 (CCL25) its cognate receptor 9 (CCR9) inhibit colorectal cancer (CRC) We found CCR9 protein expression levels were highest in colon adenomas progressively decreased invasive metastatic CRCs. was expressed both primary cultures colon-cancer-initiating (CCIC) lines derived from early-stage CRCs but not CRC. CCL25 stimulated proliferation by activating AKT signaling. In vivo, systemically injected CCR9+ CCICs led to the formation of orthotopic gastrointestinal xenograft tumors. Blocking signaling inhibited CRC native CCL25+ microenvironment, while increasing extraintestinal incidence. NOTCH signaling, which promotes metastasis, increased frequency stimulating proteasomal degradation. Overall, these data indicate progression further demonstrate an appropriate vivo experimental system study microenvironment.
elsevier.com
sci-hub.se 参考文章(67)
Silvia Fre, Danijela Vignjevic, Marie Schoumacher, Shannon L Duffy, Klaus‐Peter Janssen, Sylvie Robine, Daniel Louvard, None, Epithelial Morphogenesis and Intestinal Cancer: New Insights in Signaling Mechanisms Advances in Cancer Research. ,vol. 100, pp. 85- 111 ,(2008) , 10.1016/S0065-230X(08)00003-1
Michael P. Rettig, Pablo Ramirez, Bruno Nervi, John F. DiPersio, CXCR4 and mobilization of hematopoietic precursors. Methods in Enzymology. ,vol. 460, pp. 57- 90 ,(2009) , 10.1016/S0076-6879(09)05203-3
Culture of epithelial cells Wiley-Liss. ,(2002) , 10.1002/0471221201
Shaheen Sikandar, Diana Dizon, Xiling Shen, Zuomei Li, Jeffery Besterman, Steven M. Lipkin, The Class I Hdac Inhibitor Mgcd0103 Induces Cell Cycle Arrest and Apoptosis in Colon Cancer Initiating Cells by Upregulating Dickkopf-1 and Non-Canonical Wnt Signaling Oncotarget. ,vol. 1, pp. 596- 605 ,(2010) , 10.18632/ONCOTARGET.194
Catherine Booth, Julie A. O'Shea, Isolation and Culture of Intestinal Epithelial Cells John Wiley & Sons, Inc.. pp. 303- 335 ,(2002) , 10.1002/0471221201.CH10
Lisa S Poritz, Rosalyn B Irby, Walter A Koltun, Leonard R Harris, Danielle M Pastor, Christina L Kline, Vernon M Chinchilli, Thomas L Olson, Primary cell lines: false representation or model system? a comparison of four human colorectal tumors and their coordinately established cell lines International Journal of Clinical and Experimental Medicine. ,vol. 3, pp. 69- 83 ,(2010)
Gabriel Márquez, Rosa Varona, Ángel Zaballos, Carlos Ardavín, Julio Gutiérrez, Cutting Edge: Identification of the Orphan Chemokine Receptor GPR-9-6 as CCR9, the Receptor for the Chemokine TECK Journal of Immunology. ,vol. 162, pp. 5671- 5675 ,(1999)
I. Bozic, T. Antal, H. Ohtsuki, H. Carter, D. Kim, S. Chen, R. Karchin, K. W. Kinzler, B. Vogelstein, M. A. Nowak, Accumulation of driver and passenger mutations during tumor progression Proceedings of the National Academy of Sciences of the United States of America. ,vol. 107, pp. 18545- 18550 ,(2010) , 10.1073/PNAS.1010978107
Matthew D Johnston, Carina M Edwards, Walter F Bodmer, Philip K Maini, S Jonathan Chapman, None, Mathematical modeling of cell population dynamics in the colonic crypt and in colorectal cancer Proceedings of the National Academy of Sciences of the United States of America. ,vol. 104, pp. 4008- 4013 ,(2007) , 10.1073/PNAS.0611179104
H. Yanai, K. Nakamura, S. Hijioka, A. Kamei, T. Ikari, Y. Ishikawa, E. Shinozaki, N. Mizunuma, K. Hatake, A. Miyajima, Dlk-1, a cell surface antigen on foetal hepatic stem/progenitor cells, is expressed in hepatocellular, colon, pancreas and breast carcinomas at a high frequency. Journal of Biochemistry. ,vol. 148, pp. 85- 92 ,(2010) , 10.1093/JB/MVQ034