Induction of interleukin-6 and oncostatin M by radiation in Kaposi's sarcoma cell lines

Purpose: To define the in vitro radiosensitivity of Kaposi's sarcoma (KS) a nd to explore the mechanism of its extreme clinical radiosensitivity. Methods and Materials: The radiation survivals of the three KS cell culture s (KSY-1, KS-JD, KS6-3E) were determined by clonogenic assay and MTT assay. Supernatants from irradiated cells were collected at different time points for measurement of the interleukin 6 (IL-6), oncostatin M (OSM), and basic fibroblast growth factor (bFGF) by ELISA. Changes in the mRNA expression o f these cytokines were examined by reverse transcription polymerase chain r eaction and Southern blot hybridization. Fresh KS cells were preincubated w ith the irradiated supernatant before irradiation, and the change in surviv als were assessed. Results: The mean SF-2 (survival fraction after 2 Gy) for KS was 0.43. Prei ncubation with the irradiated supernatant reduced the SF-2 significantly fr om 0.43 to 0.33 (p < 0.05). Treatment with irradiated supernatant alone was not cytotoxic to the cells. Radiation induced IL-6 and OSM production by K S cells at the transcription level. A single dose of 2 Gy increased IL-6 an d OSM mRNA expression of the KS Y-l cells. This corresponded to an increase in the IL-6 and OSM levels in the culture medium. There was no significant change in the level of bFGF. Preincubation with recombinant human IL-6 or OSM sensitized KS in a dose dependent manner. Conclusion: The low SF-2 value for these KS cell lines correlates with the clinical radiosensitivity of KS. The high radiosensitivity may be due to ra diation induction of cytokines such as IL-6 and OSM, which are radiosensiti zers for KS cells. (C) 2001 Elsevier Science Inc.