Modulation of TcR/CD3-zeta chain expression by a circulating factor derived from ovarian cancer patients.
In women with ovarian cancer, suppression of components of the immune system may promote tumour development. Previous studies in ovarian cancer have demonstrated that decreased expression and function of the T-cell receptor (TcR)-associated signal transducing zeta-chain correlates with deficient immune responsiveness of T cells. In this study, sera and ascitic fluids obtained from woman with advanced ovarian cancer were found to suppress the expression of TcR-associated zeta chain. This suppression of zeta chain expression was dose-dependent and was not observed with biologic fluids obtained from healthy women. The factor responsible for the loss of zeta chain was purified from ascites and characterized as a protein with an appropriate molecular weight of 14 kD. Suppression of T-cell TcR-zeta was specific, since neither lck nor ZAP-70 expression was affected, while zeta chain was almost completely suppressed. This selective suppression of TcR-zeta expression by the 14 kD ascites-derived factor was shown to operate at the mRNA level. By defining the mechanism through which this protein modulates TcR-zeta chain levels, it might be possible to ultimately prevent the suppressive influences of the tumour microenvironment and restor immune competence in patients with ovarian carcinoma.
Taylor
D D
DD
Department of Obstetrics, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Bender
D P
DP
Gerçel-Taylor C
Stanson
J
J
Whiteside
T L
TL
D000328:Adult; D001201:Ascites; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007121:Immunocompetence; D007165:Immunosuppression Therapy; D008565:Membrane Proteins / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis*; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis*
D008565:Membrane Proteins; D011506:Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; C054979:antigen T cell receptor, zeta chain