Serum amyloid A induction in tumor-bearing mice: Evidence for a tumor- derived mediator

Increases in the concentration of various acute-phase serum proteins synthesized by the liver, including serum amyloid A (SAA) have been reported in cancer patients or tumor-bearing animals. The induction of SAA has been shown, from studies of endotoxin-induced inflammation, to be mediated by cytokines, including interleukins 1 and 6 (IL-1 and IL-6) and tumor necrosis factor (TNF). We have found increased SAA levels in mice transplanted with a variety of tumors, and used the S-180 sarcoma to investigate the mechanism of SAA induction of cancer; this appeared to be independent of immunogenicity since elevated SAA concentrations were also observed in tumor-bearing nude mice. The following evidence was obtained indicating that an endogenous mediator produced by the tumor was responsible for cancer-associated SAA induction: a) SAA concentrations returned to baseline after surgical removal of the tumor; b) injection of serum obtained from tumor-bearing mice into healthy mice induced SAA levels with a maximal induction 24h after injection; c) injection of supernatants from in vitro cultures of S-180 tumor cells also induced SAA in healthy mice; d) serum from tumor-bearing mice or supernatants from S-180 cell cultures was capable of inducing SAA synthesis in vitro by the human hepatoma cell line Hep3B. The putative cancer associated SAA inducer is non dialyzable, heat-labile and has a molecular mass of approximately 8-12 kD.