Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression

  • Authors:
    • Masami Watanabe
    • Yuji Kashiwakura
    • Peng Huang
    • Kazuhiko Ochiai
    • Junichiro Futami
    • Shun-Ai Li
    • Munenori Takaoka
    • Yasutomo Nasu
    • Masakiyo Sakaguchi
    • Nam-Ho Huh
    • Hiromi Kumon
  • View Affiliations

  • Published online on: March 1, 2009     https://doi.org/10.3892/ijo_00000191
  • Pages: 657-663
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Abstract

The REIC/Dkk-3 gene has been reported to be a tumor suppressor and the expression is significantly down-regulated in a broad range of cancer cell types. The protein is secretory, but the physiological function remains unclear. This study demonstrated that recombinant REIC/Dkk-3 protein induced the differentiation of human CD14+ monocytes into a novel cell type (REIC/Dkk-3Mo). REIC/Dkk-3Mo resembles immature dendritic cells generated with IL-4 and GM-CSF. Both these cell populations exhibit similar proportions of CD11c+, CD40+, CD86+ and HLA-DR+ cells and endocytic capacity, but REIC/Dkk-3Mo is negative for CD1a antigen. An analysis of the signal transducers and activators of transcription (STAT) pathways revealed that REIC/Dkk-3 induces phosphorylation of STAT 1 and STAT 3. Furthermore, intratumoral administration of REIC/Dkk-3 protein significantly suppressed tumor growth with CD11c+ and CD8+ (dendritic and killer T cell marker, respectively) cell accumulation and enhanced anti-cancer cytolytic activity of splenocytes. These data indicated a cytokine-like role of REIC/Dkk-3 protein in monocyte differentiation that might be exploited therapeutically.

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March 2009
Volume 34 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Watanabe M, Kashiwakura Y, Huang P, Ochiai K, Futami J, Li S, Takaoka M, Nasu Y, Sakaguchi M, Huh N, Huh N, et al: Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression. Int J Oncol 34: 657-663, 2009
APA
Watanabe, M., Kashiwakura, Y., Huang, P., Ochiai, K., Futami, J., Li, S. ... Kumon, H. (2009). Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression. International Journal of Oncology, 34, 657-663. https://doi.org/10.3892/ijo_00000191
MLA
Watanabe, M., Kashiwakura, Y., Huang, P., Ochiai, K., Futami, J., Li, S., Takaoka, M., Nasu, Y., Sakaguchi, M., Huh, N., Kumon, H."Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression". International Journal of Oncology 34.3 (2009): 657-663.
Chicago
Watanabe, M., Kashiwakura, Y., Huang, P., Ochiai, K., Futami, J., Li, S., Takaoka, M., Nasu, Y., Sakaguchi, M., Huh, N., Kumon, H."Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression". International Journal of Oncology 34, no. 3 (2009): 657-663. https://doi.org/10.3892/ijo_00000191