Research Papers:

Lack of interferon-γ receptor results in a microenvironment favorable for intestinal tumorigenesis

Caibo Zhang, Dong Hou, Haifeng Wei, Minnan Zhao, Lin Yang, Qiao Liu, Xiyu Zhang, Yaoqin Gong and Changshun Shao _

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Oncotarget. 2016; 7:42099-42109. https://doi.org/10.18632/oncotarget.9867

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Caibo Zhang1,2, Dong Hou1, Haifeng Wei3, Minnan Zhao1, Lin Yang4, Qiao Liu1, Xiyu Zhang1, Yaoqin Gong1, Changshun Shao1,5

1Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong, 250012, China

2Department of Life Sciences, Qilu Normal University, Jinan, Shandong, 250013, China

3First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250012, China

4Huaiyin People’s Hospital, Jinan, Shandong, 250021, China

5Department of Genetics/Human Genetics Institute of New Jersey, Piscataway, NJ, 08854, USA

Correspondence to:

Changshun Shao, email: changshun.shao@gmail.com

Keywords: IFN-γ receptor, intestinal tumorigenesis, gene expression profiling, inflammation, tumor microenvironment

Received: January 13, 2016     Accepted: May 08, 2016     Published: June 07, 2016


IFN-γ plays an important role in innate and adaptive immunity. IFN-γ signaling is also involved in tumorigenesis, with both pro- and antitumor activities documented. We here report the characterization of intestinal tumorigenesis in ApcMin/+ mice that lack IFN-γ receptor. We observed that Ifngr1−/−ApcMin/+ mice are shorter-lived than Ifngr1+/+ApcMin/+ mice. The tumors in Ifngr1−/−ApcMin/+ mice are more likely to progress into invasive adenocarcinomas. Gene expression profiling by RNA sequencing revealed a significant upregulation of genes involved in inflammation and tissue remodeling in tumors of Ifngr1−/−ApcMin/+ mice when compared to those in Ifngr1+/+ApcMin/+ mice. In particular, five genes encoding matrix metallopeptidases (MMPs) were among the upregulated. On the other hand, genes that promote or maintain intestinal differentiation, such as Cdx2, Cdhr2 and Cdhr5, were downregulated. Tumor-associated macrophages were more abundant and were more favored toward M2 polarization in Ifngr1−/−ApcMin/+ mice than in Ifngr1+/+ApcMin/+ mice. Furthermore, the Ifngr1 was significantly downregulated in intestinal tumors when compared to mucosa. A similar trend was noted for human colorectal carcinomas. Together, our results indicate that adequate IFN-γ signaling is critical for maintaining a tumor-prohibitive microenvironment.

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