Serial analysis of gene expression in progressing and regressing mouse tumors implicates the involvement of RANTES and TARC in antitumor immune responses
Related Experiment Video
Updated: Aug 7, 2026
Identification and Characterization of Metastatic Factors by Gene Transfer into the Novel RIP-Tag; RIP-tva Murine Model
Published on: October 16, 2017
Yukoh Nakazaki1, Hidenori Hase, Hiroyuki Inoue
1Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University Hospital, Kyushu University, Fukuoka 812-8582, Japan.
Abstract:
Previously we demonstrated that gene transduction of the granulocyte-macrophage colony stimulating-factor (GM-CSF) gene into mouse tumor cells eliminated tumorigenicity in vivo. The rejection process of the subcutaneous tumor was as follows: transient tumor growth peaked around 10 days after tumor injection, then the tumors were rejected within a week. In this paper, we analyzed the gene expression of the transiently established tumor masses by the serial analysis of gene expression method to identify molecules associated with the antitumor effect. We then screened those genes that were differentially expressed between the parental and the GM-CSF-transduced tumors and identified a group of genes that are suggested to have a relationship with tumor rejection, including a cytokine receptor, adhesion molecules, chemokines, cytotoxicity-related molecules, and others. Focusing on the chemokine genes TARC and RANTES, which were preferentially expressed in the GM-CSF-transduced tumors, their forced expression on mouse tumor cells showed moderate suppression of tumor formation. Transduction of GM-CSF in combination with either the TARC or the RANTES gene into tumor cells profoundly inhibited tumor establishment. Histological findings suggested the significant contribution of CD4+ T cells to tumor regression in both TARC/GM-CSF- and RANTES/GM-CSF-transduced tumor cells, in excess of that seen with GM-CSF transduction alone.
Insights
Gene transfer of granulocyte-macrophage colony-stimulating factor (GM-CSF) into tumors eliminated tumorigenicity. Combining GM-CSF with chemokines TARC or RANTES enhanced tumor rejection, involving CD4+ T cells.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Gene transduction of granulocyte-macrophage colony-stimulating factor (GM-CSF) into mouse tumor cells previously demonstrated to eliminate tumorigenicity in vivo.
- Tumor rejection followed transient growth, peaking around 10 days post-injection and resolving within a week.
Purpose of the Study:
- To identify molecules associated with the antitumor effect of GM-CSF transduction.
- To investigate the role of specific chemokine genes (TARC and RANTES) in tumor rejection.
Main Methods:
- Serial analysis of gene expression (SAGE) was employed to analyze gene expression in tumor masses.
- Differential gene expression screening between parental and GM-CSF-transduced tumors was performed.
- Forced expression of TARC and RANTES, alone and with GM-CSF, in mouse tumor cells.
Main Results:
- GM-CSF transduction led to differential expression of genes related to tumor rejection, including cytokine receptors, adhesion molecules, chemokines, and cytotoxicity-related molecules.
- Preferential expression of chemokine genes TARC and RANTES was observed in GM-CSF-transduced tumors.
- Forced expression of TARC or RANTES alone showed moderate tumor suppression; combined with GM-CSF, tumor establishment was profoundly inhibited.
- Histological analysis indicated significant CD4+ T cell involvement in tumor regression for combined TARC/GM-CSF and RANTES/GM-CSF groups.
Conclusions:
- GM-CSF gene transduction is a viable strategy for eliminating tumor growth.
- Chemokines TARC and RANTES, when co-expressed with GM-CSF, significantly enhance antitumor immunity.
- CD4+ T cells play a crucial role in the enhanced tumor regression observed with combined gene therapies.
Related Concept Videos
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
02:43Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...