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Cell expression patterns of CD147 in N-diethylnitrosamine/phenobarbital-induced mouse hepatocellular carcinoma

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Abstract

Overexpression of CD147/basigin in hepatic cells promotes the progression of hepatocellular carcinoma (HCC). Whether CD147 also expressed in liver non-parenchymal cells and associated with HCC development was unknown. The aim of the study was to explore time-dependent cell expression patterns of CD147 in a widely accepted N-diethylnitrosamine/phenobarbital (DEN/PB)-induced HCC mouse model. Liver samples collected at month 1–12 of post-DEN/PB administration were assessed the localization of CD147 in hepatocytes, endothelial cells, hepatic stellate cells, and macrophages. Immunohistochemistry analysis showed that CD147 was upregulated in liver tumors during month 1–8 of DEN/PB induction. Expression of CD147 was positively correlated with cytokeratin 18, a hepatocyte marker (r = 0.7857, P = 0.0279), CD31 (r = 0.9048, P = 0.0046), an endothelial cell marker, and CD68, a macrophage marker (r = 0.7619, P = 0.0368). A significant correlation was also observed between CD147 and alpha-smooth muscle actin (r = 0.8857, P = 0.0333) at DEN/PB initiation and early stage of tumor formation. Immunofluorescence and fluorescence in situ hybridization showed that CD147 co-expressed with cytokeratin 18, CD31, alpha-smooth muscle actin, and CD68. Moreover, there existed positive correlations between CD147 and microvessel density (r = 0.7857, P = 0.0279), CD147 and Ki-67 (r = 0.9341, P = 0.0022) in the development of DEN/PB-induced HCC. In conclusion, our results demonstrated that CD147 was upregulated in the liver parenchymal and mesenchymal cells and involved in angiogenesis and tumor cell proliferation in the development of DEN/PB-induced HCC.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81172144) and the National Science and Technology Major Project (Nos. 2012ZX10002-015 and 2012AA020806).

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All the authors declare no conflict of interest.

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Authors and Affiliations

  1. Cell Engineering Research Center and Department of Cell Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, No. 169, Changle West Road, Xi’an, 710032, China

    Meng Lu, Jiao Wu, Xi-Long Wang, Can Li, Zhi-Nan Chen & Huijie Bian

  2. Company Eight, Cadet Brigade, Fourth Military Medical University, Xi’an, 710032, China

    Feng He

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  1. Meng Lu
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  2. Jiao Wu
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Correspondence to Zhi-Nan Chen or Huijie Bian.

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Lu, M., Wu, J., He, F. et al. Cell expression patterns of CD147 in N-diethylnitrosamine/phenobarbital-induced mouse hepatocellular carcinoma. J Mol Hist 46, 79–91 (2015). https://doi.org/10.1007/s10735-014-9602-3

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