[The effect of IL-6 produced by pancreatic carcinoma cells on blood-borne metastasis to the liver: a study on in vivo nude mouse model].
Metastasis of pancreas carcinoma to the liver via the portal vein carries the gravest prognosis to patients. Using 10 cultured lines of pancreas carcinoma (PCI), established in our laboratory, we examined phenotypes that are important in hematogenous metastasis to the liver in anti-asialo GM1 treated nude mice. IL-6 production by PCI lines inversely correlated with liver metastasis, indicating that tumor-derived IL-6 may modulate metastatic competence. Therefore, we transfected human interleukin-6 cDNA in combination with the cytomegalovirus promoter to the non-IL-6 producer PCI-43, the line with the highest metastatic potential. Thus we established interleukin-6 high-, low-, and non-producer PCI-43, variant lines. Transfection itself did not endow PCI-43 line with alterations in surface phenotypes, kinesis, invasiveness, and doubling time in vitro. Metastatic potential of PCI-43 was profoundly suppressed in IL-6 high producer sublines. In mice inoculated with IL-6 high-producer PCI-43, an increase in human IL-6 in sera, as well as an appearance of PCI-43-reactive IgG was seen. The reduction in metastasis, therefore, may be mediated by antibody-dependent or complement-dependent cytotoxicity.
Saito
K
K
Second Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D004195:Disease Models, Animal; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000502:physiology; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009360:Neoplastic Cells, Circulating; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015850:Interleukin-6