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Effect of interferon-gamma and TNF-alpha on MUC1 mucin expression in ovarian carcinoma cell lines
S Clark1, M A McGuckin, T Hurst
1Department of Obstetrics and Gynaecology, University of Queensland, Royal Brisbane Hospital, Herston, Australia.
Abstract:
In view of the potential uses of cell surface tumour associated antigens in novel anticancer treatment, a study was designed to investigate whether the biological response modifiers interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) could effect the expression of an epitope on the tumour associated MUC1 epithelial mucin. Four ovarian carcinoma cell lines showing high (OAW42 and GG) and low (JAM and PE01) basal expression of MUC1 were treated with 10-1000 U/mL of IFN-gamma or TNF-alpha for one or five days. Changes in MUC1 expression in cells exposed to IFN-gamma or TNF-alpha were monitored using an ELISA technique with the monoclonal antibody BC2 which reacts with a core protein epitope on the MUC1 mucin, and then corrected for the number of viable cells present. TNF-alpha had little effect on MUC1 expression, but one or five days exposure to IFN-gamma significantly increased MUC1 expression (p < 0.01) in all cell lines including the two cell lines that initially showed little or no expression.
Insights
Interferon-gamma (IFN-gamma) significantly increased MUC1 expression in ovarian cancer cells. This finding suggests IFN-gamma
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Cell surface tumour associated antigens, like MUC1 mucin, are potential targets for novel anticancer treatments.
- Biological response modifiers such as interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are being investigated for their therapeutic potential.
Purpose of the Study:
- To investigate the effect of IFN-gamma and TNF-alpha on the expression of a MUC1 core protein epitope.
- To determine if these biological response modifiers can alter MUC1 expression in ovarian carcinoma cell lines.
Main Methods:
- Four ovarian carcinoma cell lines with varying basal MUC1 expression were treated with IFN-gamma or TNF-alpha (10-1000 U/mL) for 1 or 5 days.
- Changes in MUC1 expression were quantified using an ELISA assay with the BC2 monoclonal antibody, which targets a core protein epitope.
- Results were corrected for viable cell count.
Main Results:
- Tumour necrosis factor-alpha (TNF-alpha) demonstrated minimal impact on MUC1 expression.
- Interferon-gamma (IFN-gamma) exposure significantly increased MUC1 expression (p < 0.01) across all tested cell lines.
- This increase was observed even in cell lines with initially low or undetectable MUC1 expression after one or five days of treatment.
Conclusions:
- IFN-gamma effectively upregulates MUC1 expression in ovarian carcinoma cells, regardless of their basal MUC1 levels.
- The findings highlight IFN-gamma's potential role in modulating tumour associated antigens for therapeutic strategies.
- Targeting MUC1 expression with IFN-gamma may offer a novel approach in anticancer therapy.