Transfection of colorectal cancer cells with chemokine MCP-3 (monocyte chemotactic protein-3) gene retards tumor growth and inhibits tumor metastasis.
OBJECTIVE
To evaluate the possibility of the induction of anti-tumor immune response by transfecting the colorectal cancer 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. The tumorigenicity of wild type CMT93 and CMT93 gene transfectants were detected by in vivo experiments. The immune cell infiltrations in tumor tissue and tumor metastasis were detected histopathologically.


RESULTS
MCP-3 mRNA expression was detected by RT-PCR in gene-transfected cells (CMT93/MCP-3), but not in control groups. And MCP-3 secreted in the cell culture supernatant possessed chemotatic activity. The results from in vivo experiments showed that the tumorigenicity of CMT93/MCP-3 had not decreased, but the tumors derived from CMT93/MCP-3 cells grew more slowly than those from CMT93 cells (1.021+/-0.253) cm(2) vs (1.769+/-0.371) cm(2), P<0.05) or CMT93/mock cells (1.021+/-0.253) cm(2) vs (1.680 +/-0.643)cm(2), P<0.05). Histophathological results showed few immune cells infiltrating in the tumor tissue derived from the controls. In the tumor tissue derived from CMT93/MCP-3, infiltrating immune cells increased. In addition, no tumor metastasis was found in all mice inoculated with CMT93/MCP-3 tumor cells. But all mice had tumor metastasis in CMT93 controls and 4 in 5 mice had tumor metastasis in CMT93/mock controls.


CONCLUSIONS
The results suggested that the transfection of chemokine MCP-3 gene could promote the induction of anti-colorectal cancer immunity, but the tumor growth could not be inhibited completely by merely MCP-3 gene transfection.
Hu
Jin-Yue
JY
Lab of Tumor Immunobiology, Cancer Research Institute, Xiangya Medical School, Central South University, Hunan Province, China.
Li
Guan-Cheng
GC
Wang
Wen-Meng
WM
Zhu
Jian-Gao
JG
Li
Yue-Fei
YF
Zhou
Guo-Hua
GH
Sun
Qu-Bing
QB
D000818:Animals; D054410:Chemokine CCL7; D002633:Chemotaxis; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016207:Cytokines; D005260:Female; D015316:Genetic Therapy; D008207:Lymphatic Metastasis / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014162:Transfection
C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm