The immune system, apoptosis and apoptosis-related proteins in human ovarian tumors (a review).
Our studies on the relationships among the lymphoid system, apoptosis and apoptosis-related proteins (ARP) in human ovarian benign cysts, borderline tumors, and carcinomas are reviewed and analyzed. Fas and Fas ligand are expressed in 50% to 80% of the epithelial cells in all studied tumors. Many bcl-2-positive tumor epithelial cells are seen in benign cysts and they disappear as tumorigenesis progresses, whereas p53 protein is found only in borderline tumors and in carcinomas. Many exceptions to the opinion that bcl-2 inhibits apoptosis and p53 promotes it are encountered. Bcl-2 is lacking in epithelial cells of mucoid tumors of all grades, and its absence does not stimulate their apoptosis. P53 protein is absent from most lymphocytes, macrophages and epithelial tumor cells, nevertheless, they undergo apoptosis. Indeed, in many tumors apoptosis is regulated without the participation of bcl-2 and p53. Different components of the immune system become active during different stages of tumor development. The weak reaction of T-cell killers and macrophages is typical in benign cysts. In borderline tumors, the activity of T-cell killers increases in the parenchyma, and that of T helpers and macrophages in the stroma. In carcinomas with high lymphoid infiltration, a strong reaction of macrophages and T cell killers in the tumoral parenchyma as well high reaction of T helpers and B lymphocytes in the stroma are typical. Apoptosis that should protect against tumor also stimulates apoptotic death of lymphocytes and macrophages, and this has catastrophic consequences, as seen in weakly infiltrated carcinomas. In conclusion, our studies indicate that during malignancy the major task of the immune system is curtailment and control of tumorigenesis.
Zusman
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Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot 76100, Israel. zusman@agri.huji.il
Gurevich
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P
Gurevich
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E
Ben-Hur
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H
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007107:Immune System; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008264:Macrophages; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D014408:Biomarkers, Tumor; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor