Interleukin-2 enhances susceptibility of colon cancer cells to FasR-mediated apoptosis by up-regulating Fas receptor level and down-regulating FAP-1 expression

E. Song, J. Chen, B. Antus, M. Wang, Y. Xie, N. Ouyang, H. Yao, M. S. Exton

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Colon cancer cells are resistant to FasR-mediated apoptosis, which contributes to their evasion from immune attack by CTLs and NK cells. FasR refractoriness of the malignancies was reported to result from loss of Fas receptors and overepression of Fas-associated phosphatase-1 (FAP-1). Therefore, we investigated the effects of recombinant IL-2 on FasR and FAP-1 expression of colon cancer cells, and its influence on the sensitivity of colon cancer cells to FasR-mediated apoptosis. Colon cancer cell lines SW480, HT-29 and CaCo2 were incubated with IL-2 for different periods of time. Sensitivity of the cells to FasR-mediated apoptosis was assessed by measuring their apoptosis after treated with agonistic anti-FasR MAb CH-11. Additionally, Fas receptor levels were examined by immunofluorescence and mRNA expression of FasR and FAP-1 was investigated by RT-PCR. IL-2 incubation increased CH11-induced apoptosis in all colon cancer cell lines in a time-dependent manner. In parallel, IL-2 up-regulated Fas receptor expression on HT-29 and CaCo2 cells at both protein and mRNA levels, which were low before treatment, while it served to maintain high expression of FasR on SW480 cells. Additionally, IL-2 down-regulated FAP-1 mRNA expression on SW480 and CaCo2 cells, which was high before treatment. However, low expression of FAP-1 on HT-29 cells remained stable after IL-2 treatment. Thus, IL-2 enhances susceptibility of colon cancer cells to FasR-mediated apoptosis by up-regulating Fas receptor levels and by down-regulating FAP-1 expression, which accounts for its therapeutic effects on abolishing immune evasion in colon cancer cells.

Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalInternational Journal of Immunopathology and Pharmacology
Volume13
Issue number3
Publication statusPublished - 2000

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CD95 Antigens
Phosphoric Monoester Hydrolases
Colonic Neoplasms
Interleukin-2
Apoptosis
Immune Evasion
HT29 Cells
Messenger RNA
Cell Line
Therapeutic Uses
Natural Killer Cells
Fluorescent Antibody Technique
Therapeutics
Polymerase Chain Reaction

Keywords

  • Apoptosis
  • Colon neoplasms
  • Fas receptor
  • Fas-associated phosphatase-1
  • Interleukin-2

ASJC Scopus subject areas

  • Pharmacology

Cite this

Interleukin-2 enhances susceptibility of colon cancer cells to FasR-mediated apoptosis by up-regulating Fas receptor level and down-regulating FAP-1 expression. / Song, E.; Chen, J.; Antus, B.; Wang, M.; Xie, Y.; Ouyang, N.; Yao, H.; Exton, M. S.

In: International Journal of Immunopathology and Pharmacology, Vol. 13, No. 3, 2000, p. 113-122.

Research output: Contribution to journalArticle

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abstract = "Colon cancer cells are resistant to FasR-mediated apoptosis, which contributes to their evasion from immune attack by CTLs and NK cells. FasR refractoriness of the malignancies was reported to result from loss of Fas receptors and overepression of Fas-associated phosphatase-1 (FAP-1). Therefore, we investigated the effects of recombinant IL-2 on FasR and FAP-1 expression of colon cancer cells, and its influence on the sensitivity of colon cancer cells to FasR-mediated apoptosis. Colon cancer cell lines SW480, HT-29 and CaCo2 were incubated with IL-2 for different periods of time. Sensitivity of the cells to FasR-mediated apoptosis was assessed by measuring their apoptosis after treated with agonistic anti-FasR MAb CH-11. Additionally, Fas receptor levels were examined by immunofluorescence and mRNA expression of FasR and FAP-1 was investigated by RT-PCR. IL-2 incubation increased CH11-induced apoptosis in all colon cancer cell lines in a time-dependent manner. In parallel, IL-2 up-regulated Fas receptor expression on HT-29 and CaCo2 cells at both protein and mRNA levels, which were low before treatment, while it served to maintain high expression of FasR on SW480 cells. Additionally, IL-2 down-regulated FAP-1 mRNA expression on SW480 and CaCo2 cells, which was high before treatment. However, low expression of FAP-1 on HT-29 cells remained stable after IL-2 treatment. Thus, IL-2 enhances susceptibility of colon cancer cells to FasR-mediated apoptosis by up-regulating Fas receptor levels and by down-regulating FAP-1 expression, which accounts for its therapeutic effects on abolishing immune evasion in colon cancer cells.",
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AU - Song, E.

AU - Chen, J.

AU - Antus, B.

AU - Wang, M.

AU - Xie, Y.

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AU - Yao, H.

AU - Exton, M. S.

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AB - Colon cancer cells are resistant to FasR-mediated apoptosis, which contributes to their evasion from immune attack by CTLs and NK cells. FasR refractoriness of the malignancies was reported to result from loss of Fas receptors and overepression of Fas-associated phosphatase-1 (FAP-1). Therefore, we investigated the effects of recombinant IL-2 on FasR and FAP-1 expression of colon cancer cells, and its influence on the sensitivity of colon cancer cells to FasR-mediated apoptosis. Colon cancer cell lines SW480, HT-29 and CaCo2 were incubated with IL-2 for different periods of time. Sensitivity of the cells to FasR-mediated apoptosis was assessed by measuring their apoptosis after treated with agonistic anti-FasR MAb CH-11. Additionally, Fas receptor levels were examined by immunofluorescence and mRNA expression of FasR and FAP-1 was investigated by RT-PCR. IL-2 incubation increased CH11-induced apoptosis in all colon cancer cell lines in a time-dependent manner. In parallel, IL-2 up-regulated Fas receptor expression on HT-29 and CaCo2 cells at both protein and mRNA levels, which were low before treatment, while it served to maintain high expression of FasR on SW480 cells. Additionally, IL-2 down-regulated FAP-1 mRNA expression on SW480 and CaCo2 cells, which was high before treatment. However, low expression of FAP-1 on HT-29 cells remained stable after IL-2 treatment. Thus, IL-2 enhances susceptibility of colon cancer cells to FasR-mediated apoptosis by up-regulating Fas receptor levels and by down-regulating FAP-1 expression, which accounts for its therapeutic effects on abolishing immune evasion in colon cancer cells.

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