Interleukin 10 is expressed in human gliomas in vivo and increases glioma cell proliferation and motility in vitro.
Interleukin 10 (IL-10) is a cytokine with a broad spectrum of immunosuppressive activity, but itoffs role in the oncogenesis of solid tumors is still unclear. In previous experiments we have shown that IL-10 specific mRNA is produced within glial tumors in vivo. The aim of the present study was to investigate the expression of the IL-10 protein in vivo and to identify the cells producing IL-10 within the tumor tissue. Expression levels significantly increased with malignancy of the gliomas. 87.5% of grade III and IV, but only 4% of grade II tumors expressed high levels of mRNA. Elevation of IL-10 serum levels was found in 11% of low grade and in 63.6% of high grade glioma patients. In situ hybridization analysis with combined immunohistochemistry revealed that: a) IL-10 is not produced by infiltrating B- or T- lymphocytes, b) both microglia and astroglia contributed to IL-10 expression in malignant gliomas in vivo. These data suggested the functional role of IL-10 in glioma progression. Therefore, the effects of IL-10 on proliferation and migration of glioma cells were determined in vitro. Two human glioma cell lines were grown as monolayer as well as spheroids in the presence of different concentrations of IL-10. IL-10 increased cell proliferation significantly in both culture systems with a dose optimum of 25 ng/ml. Glioma cell motility was enhanced with 25 ng/ml as the optimal dose. Adding the IL-10 specific antibody reversed both effects. We conclude from our data that IL-10 is involved in the progression of glial tumors, especially in the enhancement of tumor cell proliferation and migration which promotes infiltration of the surrounding tissue.
Huettner
C
C
Institute of Pathology, University of Wuerzburg, Germany.
Czub
S
S
Kerkau
S
S
Roggendorf
W
W
Tonn
J C
JC
D001921:Brain / Q000196:embryology; D002455:Cell Division; D002465:Cell Movement; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D016753:Interleukin-10 / Q000378:metabolism*; D009940:Organoids; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016753:Interleukin-10