Serial analysis of gene expression in progressing and regressing mouse tumors implicates the involvement of RANTES and TARC in antitumor immune responses.
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.
Nakazaki
Yukoh
Y
Division of Molecular and Clinical Genetics, Medical Institute of Bioregulation, Kyushu University Hospital, Kyushu University, Fukuoka 812-8582, Japan.
Hase
Hidenori
H
Inoue
Hiroyuki
H
Beppu
Yoshihito
Y
Meng
Xin K
XK
Sakaguchi
Gaku
G
Kurita
Ryo
R
Asano
Shigetaka
S
Nakamura
Yusuke
Y
Tani
Kenzaburo
K
D000818:Animals; D045744:Cell Line, Tumor; D054414:Chemokine CCL17; D018946:Chemokine CCL5 / Q000235:genetics*; D019742:Chemokines, CC / Q000235:genetics*; D018450:Disease Progression; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D014158:Transcription, Genetic / Q000235:genetics
C499538:Ccl17 protein, mouse; D054414:Chemokine CCL17; D018946:Chemokine CCL5; D019742:Chemokines, CC; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor