Induction of interleukin-6 and oncostatin M by radiation in Kaposi's sarcoma cell lines.
OBJECTIVE
To define the in vitro radiosensitivity of Kaposi's sarcoma (KS) and to explore the mechanism of its extreme clinical radiosensitivity.


METHODS
The radiation survivals of the three KS cell cultures (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 of these cytokines were examined by reverse transcription polymerase chain reaction and Southern blot hybridization. Fresh KS cells were preincubated with the irradiated supernatant before irradiation, and the change in survivals were assessed.


RESULTS
The mean SF-2 (survival fraction after 2 Gy) for KS was 0.43. Preincubation with the irradiated supernatant reduced the SF-2 significantly from 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 KS cells at the transcription level. A single dose of 2 Gy increased IL-6 and OSM mRNA expression of the KS Y-1 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.


CONCLUSIONS
The low SF-2 value for these KS cell lines correlates with the clinical radiosensitivity of KS. The high radiosensitivity may be due to radiation induction of cytokines such as IL-6 and OSM, which are radiosensitizers for KS cells.
Hong
A
A
Department of Radiation Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. ahong@email.cs.nsw.gov.au
Zhang
M
M
Leigh
B
B
Stevens
G
G
D015139:Blotting, Southern; D002470:Cell Survival / Q000528:radiation effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000528:radiation effects; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000528:radiation effects; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D053683:Oncostatin M; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D011836:Radiation Tolerance / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D015850:Interleukin-6; C508351:OSM protein, human; D010455:Peptides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D053683:Oncostatin M