Effects of interferon gamma on the proliferation and modulation of cell-surface structures of human ovarian carcinoma cell lines.
Platinum-containing regimens are very effective in the primary treatment of ovarian cancer. However, upon subsequent treatment most tumors develop multidrug resistance. The clinical application of biological response modifiers like interferon gamma (IFN gamma) in advanced ovarian cancer is therefore of increasing interest. Permanent ovarian cancer cell lines are suitable for investigating the mode of action and the potential clinical effectiveness of such response modifiers. IFN gamma is known to modulate many cellular functions. In this study it was compared for its antiproliferative and antigen-modulatory activity on the expression of tumor-associated (CA-125, HMFG, CEA) and major histocompatibility complex (MHC) class I and II antigens as well as of the epidermal growth factor (EGF) receptor on 20 newly established human ovarian carcinoma cell lines. IFN gamma in concentrations of 10, 50 and 100 U/ml was used to study its antigen-modulatory effect, and at additional 1 U/ml and 1000 U/ml to assess its antiproliferative effect on the cells. The cells were incubated with IFN for 4 days. Two cell lines showed strong antiproliferative activity even at minimal doses (up to 50 U/ml). Intermediate growth inhibition between 34% and 84% was observed in 15 cell lines with higher doses. Three lines were resistant to IFN gamma. Independent of the antiproliferative effect, IFN gamma enhanced the expression of MHC class I and MHC class II in nearly all cell lines. Upregulation was also observed for most of the tumor-associated antigens (TAA) and EGF receptor expression. A down-regulation was noticed but rarely. The fact that IFN gamma showed an antiproliferative activity on the majority of the cell lines is of clinical relevance. The in vitro modulation of cell-surface determinants by IFN gamma warrants special attention. The enhanced expression of TAA and MHC antigens can improve immunogenicity of the tumor cells and may explain the therapeutic effects observed under IFN therapy in ovarian cancer. By contrast, enhanced expression of the EGF receptor, often associated with poor patient survival rates, may be an undesirable side-effect of IFN therapy.
Möbus
V J
VJ
Department of Obstetrics and Gynecology, University of Ulm, Germany.
Asphal
W
W
Knapstein
P G
PG
Kreienberg
R
R
D000951:Antigens, Neoplasm / Q000187:drug effects*; D000954:Antigens, Surface / Q000187:drug effects*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D066246:ErbB Receptors / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006680:HLA Antigens / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000648:ultrastructure; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015295:Antigens, Tumor-Associated, Carbohydrate; D006680:HLA Antigens; D011994:Recombinant Proteins; D007371:Interferon-gamma; D066246:ErbB Receptors