Expression of cytokine genes or proteins and signaling molecules in lymphocytes associated with human ovarian carcinoma.
We have reported that tumor-associated T or natural killer (NK) lymphocytes purified from ascites of women with ovarian carcinoma show defective expression and function of signaling proteins, including reduced expression of TcR-zeta chains and p56(lck). In this study, the cytokine profiles of both tumor cells and tumor-associated lymphocytes (TAL) recovered from the tumor milieu were examined. Expression of cytokine genes was studied by semi-quantitative RT-PCR and Southern hybridization, and the presence of intracellular cytokine proteins was confirmed by immunostaining. Levels of mRNA encoding the cytokine genes typically transcribed in activated T lymphocytes, including IFN-gamma, IL-2 and IL-4, were markedly reduced, as was expression of the corresponding proteins, in TAL-T or TAL-NK cells relative to normal PBL-T or PBL-NK cells, respectively. Levels of TGF-beta and IL-6 were unaltered, while those of IL-10 were up-regulated. Although both tumor cells and TALs contributed to the enhanced level of IL-10 expression, a higher proportion of TAL-T lymphocytes than normal PBL-T cells expressed IL-10 protein. The altered profile of cytokine genes and proteins in TALs, TAL-T or TAL-NK cells was associated with impaired expression and/or function of signaling molecules, zeta chain and p56(lck). Our data suggest that abnormalities in signal transduction commonly seen in lymphocytes obtained from the tumor micro-environment are related to the concomitantly observed altered patterns of expression of cytokine transcripts and proteins.
Department of Pathology, University of Pittsburgh School of Medicine, PA, USA.
H
H
Rabinowich
Y
Y
Suminami
T E
TE
Reichert
P
P
Crowley-Nowick
M
M
Bell
R
R
Edwards
T L
TL
Whiteside
D000328:Adult; D000368:Aged; D001706:Biopsy; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D021382:Protein Sorting Signals / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology
D016207:Cytokines; D021382:Protein Sorting Signals