Complement-inhibiting effect of ovarian cancer antigen CA-125.
Malignant transformation of ovarian cells of surface epithelial origin is associated with expression of a membrane-spanning glycoprotein, cancer antigen (CA)-125. The bulk of the putative CA-125 molecule is comprised a very large, folded, multivalent, mucin-like exodomain. That the extracellular motif of CA-125 exerts immunosuppressive effects which promote tumor progression has been suggested. We report that CA-125 attenuates complement lysis of antibody-sensitized cells. The secreted form of CA-125 derived from culture medium of the human ovarian adenocarcinoma cell line OVCAR-3 caused a dose-response inhibition of sheep erythrocyte hemolysis. Moreover, OVCAR-3 cells became prone to complement attack (trypan blue uptake) mediated by a gonadotropin-releasing hormone receptor antibody when (membrane-bound) CA-125 was excised/removed by trypsin/washing; this effect was counteracted by replacement with (soluble) CA-125. It is conceivable that CA-125 entraps/sheds effectors of the complement cascade.
Reproductive Biology Program, University of Wyoming, Laramie, WY 82071, USA. wmurdoch@uwyo.edu
William J
WJ
Murdoch
Edward A
EA
Van Kirk
Anna McDonnel
AM
Smedts
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D018394:CA-125 Antigen / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000276:immunology*; D003167:Complement Activation / Q000187:drug effects*; D015941:Complement Hemolytic Activity Assay; D051056:Complement Inactivating Agents / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D006461:Hemolysis; D006801:Humans; D010051:Ovarian Neoplasms; D011966:Receptors, LHRH / Q000276:immunology; D012756:Sheep; D013997:Time Factors
D000906:Antibodies; D018394:CA-125 Antigen; D051056:Complement Inactivating Agents; D011966:Receptors, LHRH