[Active immunity for anti-colorectal cancer induced by chemokine MCP-3 gene transfection].
OBJECTIVE
Chemokines play an important role in the infiltration of immune cells to tumor tissues. Anti-tumor immune response had been elicited in many tumor models by the chemokine gene transfection. The aim of this study was to evaluate the possibility of inducing anti-colorectal cancer active immune response by transfection of mouse colorectal cancer CMT93 cells with chemokine MCP-3 gene.


METHODS
Mouse MCP-3 gene was transduced into mouse colorectal cancer cells CMT93 by using of liposome. G418-resistant clones were selected and the MCP-3 mRNA expression was detected by RT-PCR. The chemotactic activity of MCP-3 in the cell culture supernatant was detected by chemotaxis assay. In vivo experiments were performed to observe the tumorigenicity of wild type CMT93 and MCP-3 gene modified tumor cells. The immune cell infiltration in tumor tissues and tumor metastasis were detected histopathologically.


RESULTS
RT-PCR detection showed MCP-3 was expressed in MCP-3 gene-transfected G418-resistant clones(CMT93/MCP-3), but not in wild type CMT93. In chemotaxis assay, the results showed that the cell culture supernatant of CMT93/MCP-3 possess obviously chemotactic activity. The chemotactic index of the CMT93/MCP-3 supernatant was 5.57(P < 0.05). The supernatants from the control groups did not possessed the chemotactic activity. In vivo experiments showed that the tumorigenicity of CMT93/MCP-3 had not decreased significantly compared to wild type CMT93, but the tumors grew more slowly from CMT93/MCP-3 than from the controls (P < 0.05). In the tumor tissue from CMT93/MCP-3, obvious infiltrated immune cells were found, and few immune cells infiltrated in the tumor tissue from the controls. In the mice inoculated with CMT93/MCP3 tumor cells, tumor metastasis was inhibited significantly, its metastasis rate was 0(0/7), lower than that of CMT93 (100%, 4/4) and CMT93/mock (80%, 4/5) (P < 0.05).


CONCLUSIONS
Transfection with chemokine MCP-3 gene can induce anti-colorectal cancer active immune response, but the tumor growth cannot be inhibited completely by merely MCP-3 gene transfection.
Hu
Jin-yue
JY
Cancer Research Institute, Xiangya Medical School, Central South University, Changsha 410078, P. R. China.
Li
Guan-cheng
GC
Zhu
Jian-gao
JG
Wang
Wen-meng
WM
Li
Yue-hui
YH
Zhou
Guo-hua
GH
Sun
Qu-bing
QB
D000818:Animals; D054410:Chemokine CCL7; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology; D016207:Cytokines; D005260:Female; D007110:Immunity, Active; D008207:Lymphatic Metastasis / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics / Q000276:immunology*; D009368:Neoplasm Transplantation / Q000276:immunology / Q000473:pathology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins