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TNF-mediated cytotoxicity and resistance in human prostate cancer cell lines
Y Nakajima1, A M DelliPizzi, C Mallouh
1Department of Urology, New York Medical College, Valhalla 10595, USA.
Background:
The contribution of TNF receptor (TNF-R) expression was investigated with respect to TNF sensitivity or insensitivity for androgen-dependent and androgen-independent human prostate cancer (PCA) cell lines, respectively.
Methods:
Flow cytometric analyses using monoclonal antibodies against the 55-kDa receptor (TNF-R1) and the 75-kDa receptor (TNF-R2) indicated that both receptors were expressed on all three cell lines.
Results:
Moreover, expression of TNF-R1 was greater than expression of TNF-R2 in these PCA cells. All three PCA cell lines produced IL-6. However, IL-6 production was enhanced when TNF-insensitive JCA-1 and PC-3 cells, but not TNF-sensitive LNCaP cells, were treated with rTNF (10(-9) M).
Conclusions:
These data suggest that the lack of an antiproliferative effect of rTNF on the androgen-independent PCA cell lines PC-3 and JCA-1 is not due to the failure of these cells to express TNF-R, but may be related to the differences in TNF-mediated IL-6 expression by these PCA cell lines.
Insights
Tumor necrosis factor receptor (TNF-R) expression was studied in prostate cancer (PCA) cells. Androgen-independent PCA cells showed enhanced IL-6 production with TNF-R stimulation, suggesting this impacts TNF sensitivity.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Investigated the role of Tumor Necrosis Factor Receptor (TNF-R) expression in prostate cancer (PCA) cell sensitivity to TNF.
- Examined both androgen-dependent and androgen-independent human PCA cell lines.
Purpose of the Study:
- To determine if TNF-R expression levels correlate with TNF sensitivity or insensitivity in prostate cancer.
- To explore the mechanism behind TNF insensitivity in certain prostate cancer cell lines.
Main Methods:
- Utilized flow cytometry with monoclonal antibodies to detect TNF-R1 (55-kDa) and TNF-R2 (75-kDa) expression.
- Analyzed Interleukin-6 (IL-6) production in response to recombinant TNF (rTNF) treatment.
Main Results:
- Both TNF-R1 and TNF-R2 were expressed on all tested PCA cell lines, with higher TNF-R1 expression.
- All PCA cell lines produced IL-6.
- TNF-insensitive JCA-1 and PC-3 cells exhibited enhanced IL-6 production upon rTNF treatment, unlike TNF-sensitive LNCaP cells.
Conclusions:
- The lack of antiproliferative effect of rTNF on androgen-independent PC-3 and JCA-1 cells is not due to absent TNF-R expression.
- Differences in TNF-mediated IL-6 expression may explain the varying TNF sensitivity observed in prostate cancer cell lines.