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Updated: Jun 25, 2026
Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
Published on: May 31, 2018
Immunological aspects of REIC/Dkk-3 in monocyte differentiation and tumor regression
Masami Watanabe1, Yuji Kashiwakura, Peng Huang
1Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University, Okayama 700-8558, Japan. mwcorrespondence@gmail.com
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.
Insights
REIC/Dkk-3 protein promotes monocyte differentiation into a novel cell type resembling dendritic cells. This protein suppressed tumor growth and enhanced anti-cancer immunity, suggesting therapeutic potential.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- The REIC/Dkk-3 gene acts as a tumor suppressor with down-regulated expression in various cancers.
- The physiological function of the secretory REIC/Dkk-3 protein is not well understood.
Purpose of the Study:
- To investigate the function of REIC/Dkk-3 protein in monocyte differentiation.
- To evaluate the therapeutic potential of REIC/Dkk-3 protein in cancer treatment.
Main Methods:
- Recombinant REIC/Dkk-3 protein was used to induce differentiation of human CD14+ monocytes.
- Characterization of the novel REIC/Dkk-3Mo cell type and comparison with immature dendritic cells.
- Analysis of STAT pathway activation.
- Intratumoral administration of REIC/Dkk-3 protein in a tumor model.
Main Results:
- REIC/Dkk-3 induced differentiation of monocytes into REIC/Dkk-3Mo, resembling immature dendritic cells (CD11c+, CD40+, CD86+, HLA-DR+).
- REIC/Dkk-3Mo cells were negative for CD1a antigen and activated STAT 1 and STAT 3 pathways.
- Intratumoral REIC/Dkk-3 suppressed tumor growth, increased CD11c+ and CD8+ cell accumulation, and enhanced splenocyte anti-cancer activity.
Conclusions:
- REIC/Dkk-3 protein exhibits a cytokine-like role in monocyte differentiation.
- REIC/Dkk-3 demonstrates potential as a therapeutic agent for cancer treatment due to its immunomodulatory and anti-tumor effects.
