Cytokine associated sensitivity of colon carcinoma cells to FasR-mediated cytotoxicity of CTL.
BACKGROUND
Resistance of colon cancer cells to FasR-mediated apoptosis due to loss of Fas receptors and overepression of Fas-associated phosphatase-1 (FAP-1) contributes to their evasion from immune attack by CTLs and NK cells. 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.


METHODS
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.


RESULTS
IL-2 incubation increased CH11-induced apoptosis in all colon cancer cell lines in a time-dependent manner (P < 0.05). In parallel, IL-2 up-regulated Fas receptor expression on HT-29 and CaCo2 cells at both protein and mRNA levels (P < 0.05), which were low before treatment, while high expression of FasR on SW480 cells remained unchanged. Additionally, IL-2 down-regulated FAP-1 mRNA expression on SW480 and CaCo2 cells, which was high before treatment (P < 0.05). However, low expression of FAP-1 on HT-29 cells remained stable after IL-2 treatment.


CONCLUSIONS
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.
Chen
Jisheng
J
Department of Surgery, Sun-Yat-Sen Memorial Hospital, Sun-Yat-Sen University of Medical Science, Guangzhou, People's Republic of China.
Zhang
Hongwei
H
Su
Fengxi
F
Min
Jun
J
Zhang
Jie
J
Song
Erwei
E
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D054645:Protein Phosphatase 1; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D007376:Interleukin-2; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019014:fas Receptor; D054645:Protein Phosphatase 1; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases