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

Masami Watanabe, Yuji Kashiwakura, Peng Huang, Kazuhiko Ochiai, Junichiro Futami, Shun Ai Li, Munenori Takaoka, Yasutomo Nasu, Masakiyo Sakaguchi, Nam Ho Huh, Hiromi Kumon

Research output: Contribution to journalArticle

44 Citations (Scopus)

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 anticancer cytolytic activity of splenocytes. These data indicated a cytokine-like role of REIC/Dkk-3 protein in monocyte differentiation that might be exploited therapeutically.

Original languageEnglish
Pages (from-to)657-663
Number of pages7
JournalInternational Journal of Oncology
Volume34
Issue number3
DOIs
Publication statusPublished - 2009

Fingerprint

Monocytes
Neoplasms
Proteins
STAT1 Transcription Factor
STAT3 Transcription Factor
HLA-DR Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
Transducers
Interleukin-4
Dendritic Cells
Phosphorylation
Cytokines
T-Lymphocytes
Growth
Population
Genes

Keywords

  • Anti-cancer immune
  • Dendritic cell
  • Dkk-3
  • Monocyte
  • REIC

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression. / Watanabe, Masami; Kashiwakura, Yuji; Huang, Peng; Ochiai, Kazuhiko; Futami, Junichiro; Li, Shun Ai; Takaoka, Munenori; Nasu, Yasutomo; Sakaguchi, Masakiyo; Huh, Nam Ho; Kumon, Hiromi.

In: International Journal of Oncology, Vol. 34, No. 3, 2009, p. 657-663.

Research output: Contribution to journalArticle

Watanabe, Masami ; Kashiwakura, Yuji ; Huang, Peng ; Ochiai, Kazuhiko ; Futami, Junichiro ; Li, Shun Ai ; Takaoka, Munenori ; Nasu, Yasutomo ; Sakaguchi, Masakiyo ; Huh, Nam Ho ; Kumon, Hiromi. / Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression. In: International Journal of Oncology. 2009 ; Vol. 34, No. 3. pp. 657-663.
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