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Updated: Aug 16, 2026
Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence
Published on: November 2, 2014
Potent suppression of natural killer cell response mediated by the ovarian tumor marker CA125
Manish S Patankar1, Yu Jing, Jamie C Morrison
1Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 600 Highland Avenue, H4/657 CSC, Madison, WI 53792-6188, USA. patankar@wisc.edu
Objectives:
CA125 expresses specific oligosaccharides that can inhibit the cytotoxicity of human natural killer (NK) cells. The current study was undertaken to determine the ability of CA125 to modulate NK cell-mediated cytotoxicity.
Methods:
CA125 was isolated from OVCAR-3 cells and its purity was determined by ELISA and ultra-sensitive mass spectrometric analysis. Peripheral blood-derived NK were treated with CA125 and standard cytotoxicity assays were performed using 51Cr-labeled K562 cells as targets. The expression of cell surface and intracellular markers on NK cells was determined by either flow cytometry or Western blot analysis.
Results:
NK cells incubated with CA125 for 72 h exhibited a 50-70% decrease in the lysis of K562 targets. Incubation with CA125 for 4 h and 24 h had no effect on NK-mediated cytolysis. Inhibition of NK function was observed at CA125 concentrations (10,000-100,000 U/ml) that are expected to be significantly lower than those observed in the tumor microenvironment. Co-stimulation with IL-2 did not abrogate the NK inhibitory response of CA125. CA125 did not reduce proliferation or induce apoptosis of NK cells and alter the expression of p56lck, phospholipase Cgamma1, ZAP70, or CD3zeta. CA125 did, however, induce major downregulation of CD16 and minor decrease in expression of CD94/NKG2A.
Conclusions:
Our ongoing research and recent work performed by other laboratories highlights the potential physiologic role of this mucin. Based on the data presented here, it is likely that the tumor-derived CA125 acts as a suppressor of the immune response that is directed against the ovarian tumors.
Insights
Tumor-associated antigen CA125 inhibits natural killer (NK) cell cytotoxicity, suppressing anti-tumor immunity. This immune suppression occurs via downregulation of key NK cell receptors, suggesting a role for CA125 in ovarian tumor immune evasion.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Biology
Background:
- CA125 (Cancer Antigen 125) is a tumor marker associated with ovarian cancer.
- CA125 possesses specific oligosaccharides that can inhibit natural killer (NK) cell activity.
- NK cells are crucial components of the innate immune system, responsible for eliminating tumor cells.
Purpose of the Study:
- To investigate the ability of CA125 to modulate NK cell-mediated cytotoxicity.
- To understand the mechanisms by which CA125 might impact NK cell function.
Main Methods:
- CA125 was isolated and purified from OVCAR-3 cells.
- NK cell cytotoxicity assays were performed using 51Cr-labeled K562 cells as targets.
- Flow cytometry and Western blot analysis were used to assess NK cell surface and intracellular markers.
Main Results:
- Incubation with CA125 for 72 hours significantly decreased NK cell lysis of K562 targets by 50-70%.
- CA125 induced downregulation of CD16 and CD94/NKG2A receptors on NK cells.
- CA125 did not affect NK cell proliferation, apoptosis, or the expression of key signaling molecules like CD3zeta.
Conclusions:
- Tumor-derived CA125 likely acts as an immune suppressor against ovarian tumors.
- CA125's inhibition of NK cell cytotoxicity may contribute to tumor immune evasion.
- Further research into CA125's role in the tumor microenvironment is warranted.
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