Reduced invasiveness and metastasis of Chinese hamster ovary cells transfected with human interleukin-17 gene

Human IL-17 (hIL-17) stimulates epithelial, endothelial fibroblastic cells and macrophages to secrete various cytokines. The present study was designe d to assess the effects of the transfection of the hIL-17 gene in Chinese h amster ovary (CHO) cells. A complementary DNA (cDNA)-encoding hIL-17 was ob tained by polymerase chain reaction (PCR) amplification from human CD4(+) T -cell cDNA and inserted into the plasmid pRc/CMV to construct an expression vector for hIL-17. CHO cells were transduced with hIL-17 DNA-carrying cyto megalovirus (CMV)-based retroviral vectors. A clone with a high mRNA expres sion of hIL-17 (CHO/IL-17) was selected by Northern blotting. There was no significant difference in the in vitro growth of cells among parent CHO cel ls, vector only transfected cells (CHO/neo) and CHO/IL-17 cells. A Matrigel invasion chamber assay, however; demonstrated significantly lowe, invasive ness by CHO/IL-17 cells than by either the parent CHO or the CHO/neo cells. There was no difference in the in vivo growth among the cells, when subcut aneously transplanted into nude mice. When injected into the tail vein, how ever; the number of metastatic nodules in the lungs of CHO/IL-17-injected m ice was significantly smaller than that of CHO- or CHO/neo-injected mice. F urthermore, NK activity of spleen cells was significantly higher in nude mi ce transplanted with CHO/IL-17 cells than in mice transplanted with pal ent CHO or CHO/neo cells. In conclusion, the hIL-17-gene-transfected CHO cells showed a significantly lower metastatic potential to the lung by directly modulating the invasiveness and metastasis of CHO cells as well as by enhan cing NK activity.