INTERLEUKIN-6 PRODUCED BY PANCREATIC-CARCINOMA CELLS ENHANCES HUMORALIMMUNE-RESPONSES AGAINST TUMOR-CELLS - A POSSIBLE EVENT IN TUMOR-REGRESSION

Production of interleukin-6 (IL-6) by human pancreatic carcinoma cells inversely correlates with potentials for blood-borne metastasis to th e liver in nude mice. IL-6 cDNA was transfected to PCI-43, one of our cultured pancreatic carcinoma cell lines that does not produce IL-6 an d generates numerous metastases to the liver. An IL-6 high-producer cl one (PCI-43h) generated few metastases; IL-6 production thus has a dir ect effect on metastasis, whereas other transfectants (PCI-43l and PCI -43n), which are IL-6 low-, and IL-6 non-producers, respectively, did generate metastases. Tumor-reactive IgG, which mediated antibody-depen dent cellular cytotoxicity (ADCC) in vitro, was detected in sera from recipient nude mice inoculated with PCI-43h but not in sera from mice given PCI-43l, PCI-43n or parent PCI-43. Tumor-reactive IgM was detect ed in sera from all mice, irrespective of inoculated PCI-43 species, w ith a slight augmentation being noted in PCI-43h-inoculated nude mice. Severe combined immunodeficiency (SCID) beige mice were then used as recipients for PCI-43 species, and tumorigeneity was examined by s.c. inoculation of a suboptimal number of PCI-43 transfectants (1 X 10(6)/ 0.1 ml). Only PCI-43h formed palpable masses in SCID beige mice, where as it first grew to be palpable but subsequently became not palpable i n nude mice, thereby revealing a dual action of tumor-derived IL-6. Th us, tumor-derived IL-6 confers growth promotion in SCID beige mice, wh ile the same cytokine exhibits anti-tumorigenic functions, presumably through humoral immune responses, in nude mice. (C) 1998 Wiley-Liss, I nc.