Differential effects of high-dose gamma irradiation on the production of transforming growth factor-beta in fresh and established human ovarian cancer.
Tumor cells from five freshly isolated ovarian tumors and four established human ovarian carcinoma cell lines were analyzed for the production of the immunoinhibitory cytokine transforming growth factor-beta (TGF-beta) before and after exposure to gamma irradiation and/or the cytokines TNF-alpha plus IFN-gamma. All fresh tumors secreted high levels of TGF-beta when compared to the levels produced by the established ovarian carcinoma cell lines. TGF-beta produced by fresh tumors was significantly reduced after high doses of gamma irradiation (10,000 cGy). In contrast with the established cell lines, irradiation significantly increased TGF-beta secretion. Exposure of fresh tumor cells to cytokines followed by irradiation caused significant reduction of TGF-beta released when compared to the amount released after exposure to cytokines only. However, in the established cell lines, cytokines followed by irradiation again significantly increased TGF-beta production. These data indicate that high doses of irradiation in fresh ovarian tumors, unlike established ovarian carcinoma cell lines, can significantly reduce the local production of this potent immunoinhibitory cytokine. This effect could work to further amplify weak immunological responses within the tumor. In addition, these findings indicate major differences between fresh tumor samples and established cell lines and warn against the sole use of continuous cell lines as models for tumors growing in vivo.
Santin
A D
AD
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717, USA.
Hiserodt
J C
JC
DiSaia
P J
PJ
Pećorelli
S
S
Granger
G A
GA
D000970:Antineoplastic Agents / Q000627:therapeutic use; D005260:Female; D005720:Gamma Rays; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
D000970:Antineoplastic Agents; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma