Differential production of interleukin 6 in human osteosarcoma cells and the possible effects on neoplastic bone metabolism

Abstract

Interleukin 6 (IL-6) exerts well-established effects on cells of the immune system as well as on various other cell types. We have investigated the effects of IL-6 produced by human osteosarcoma cells on tumor cells from two clonal human osteosarcoma cell lines, KSU.C3 and NOS-1.C8. We were unable to identify any effects of IL-6 such as cell proliferation, alkaline phosphatase activity, osteocalcin production, or collagen synthesis on the bone-forming phenotypes. However, the KSU.C3 cell line, which showed a little osteoid and no bone formation and was accompanied by a few osteoclasts in the xenografted tumors, produced high levels of IL-6, the production of which was quickly and easily stimulated by various agents. On the other hand, the NOS1.C8 cell line, which formed abundant osteoid or bone and was accompanied by no osteoclasts in the xenografted tumors, produced no detectable levels of IL-6 without stimulation, and the production of IL-6 in response to IL-lβ was slower. Our data suggest that IL-6 produced by osteosarcoma cells does not play an important role in bone formation, but may mediate osteoclastic bone resorption.