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Open AccessArticle

Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide

1
Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama 700-8530, Japan
2
Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Okayama University, Okayama 700-8530, Japan
3
Department of Oral Biochemistry, School of Dentistry, Asahi University, Gifu 501-0223, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(4), 1261; https://doi.org/10.3390/ijms19041261
Received: 26 March 2018 / Revised: 14 April 2018 / Accepted: 20 April 2018 / Published: 23 April 2018
(This article belongs to the Section Biochemistry)
T cell-deficient mice such as nude mice are often used to generate tumor xenograft for the development of anticancer agents. However, the functionality of the other immune cells including macrophages, dendritic cells (DCs), and myeloid-derived suppressor cells (MDSCs) in the xenograft are largely unknown. Macrophages and dendritic cells (DCs) acquire functionally distinct properties in response to various environmental stimuli; the interaction of these cells with MDSCs in tumor microenvironments regulates cancer progression. Nude mice are less likely to reject human cancer cells because of major histocompatibility complex (MHC) mismatches. The tumor microenvironment in a xenograft, comprising human and mouse cells, exhibits more complex bidirectional signaling and function than that of allograft. Here, we evaluated the differences of myeloid cells between them. Plasma interferon-γ and interleukin-18 concentrations in the xenograft tumor model after lipopolysaccharide (LPS) administration were significantly higher than those in the allograft tumor model. MHC class I, II, and CD80 expression levels were increased in CD11b+ and MDSC populations after LPS administration in the spleen of a xenograft tumor model but not in that of an allograft tumor model. Additionally, the number of CD80- and mannose receptor C type 1 (MRC1)-expressing cells was decreased upon LPS administration in the tumor of the xenograft tumor. These results suggest that functions of macrophages and DCs are sustained in the xenograft, whereas their functions in response to LPS were suppressed in the allograft. The findings will encourage the consideration of the effects of myeloid cells in the xenograft for drug development. View Full-Text
Keywords: myeloid-derived suppressor cells (MDSCs); dendritic cells (DCs); M1 macrophages; M2 macrophages; xenograft tumor; allograft tumor; lipopolysaccharide (LPS) myeloid-derived suppressor cells (MDSCs); dendritic cells (DCs); M1 macrophages; M2 macrophages; xenograft tumor; allograft tumor; lipopolysaccharide (LPS)
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Masuda, J.; Shigehiro, T.; Matsumoto, T.; Satoh, A.; Mizutani, A.; Umemura, C.; Saito, S.; Kijihira, M.; Takayama, E.; Seno, A.; Murakami, H.; Seno, M. Cytokine Expression and Macrophage Localization in Xenograft and Allograft Tumor Models Stimulated with Lipopolysaccharide. Int. J. Mol. Sci. 2018, 19, 1261.

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