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Int. J. Mol. Sci. 2017, 18(5), 1058;

Osteopontin Deficiency Suppresses Intestinal Tumor Development in Apc-Deficient Min Mice

Central Animal Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Division of Pathology, National Institute of Health Science, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan
Author to whom correspondence should be addressed.
Academic Editors: Takuji Tanaka and Masahito Shimizu
Received: 29 March 2017 / Revised: 5 May 2017 / Accepted: 9 May 2017 / Published: 14 May 2017
(This article belongs to the Special Issue Inflammation and Cancer)
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Osteopontin (OPN) is a secreted phosphoglycoprotein, and is a transcriptional target of aberrant Wnt signaling. OPN is upregulated in human colon cancers, and is suggested to enhance cancer progression. In this study, the effect of deficiency of OPN on intestinal tumor development in Apc-deficient Min mice was investigated. At 16 weeks of age, the number of small intestinal polyps in Min/OPN(+/−) and Min/OPN(−/−) mice was lower than that of Min/OPN(+/+) mice. Colorectal tumor incidences and multiplicities in Min/OPN(+/−) and Min/OPN(−/−) mice were significantly lower than those in Min/OPN(+/+) mice, being 48% and 0.6 ± 0.8, 50% and 0.8 ± 0.9 vs. 80% and 1.6 ± 1.7, respectively. OPN expression in colorectal tumors was strongly upregulated in Min/OPN(+/+) compared to adjacent non-tumor parts, but was decreased in Min/OPN(+/−) and not detected in Min/OPN(−/−). Targets of OPN, matrix metalloproteinases (MMPs)-3, -9, and -13 were lowered by OPN deficiency. Macrophage marker F4/80 in colorectal tumors was also lowered by OPN deficiency. MMP-9 expression was observed in tumor cells and tumor-infiltrating neutrophils. These results indicate that induction of OPN by aberrant Wnt signaling could enhance colorectal tumor development in part by upregulation of MMP-3, -9, and -13 and infiltration of macrophage and neutrophils. Suppression of OPN expression could contribute to tumor prevention, but complete deficiency of OPN may cause some adverse effects. View Full-Text
Keywords: osteopontin; colorectal tumor; macrophage osteopontin; colorectal tumor; macrophage

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Ishigamori, R.; Komiya, M.; Takasu, S.; Mutoh, M.; Imai, T.; Takahashi, M. Osteopontin Deficiency Suppresses Intestinal Tumor Development in Apc-Deficient Min Mice. Int. J. Mol. Sci. 2017, 18, 1058.

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