Influence of cytokines on the expression of fas ligand and CD44 splice variants in colon carcinoma cells.
The expression of Fas ligand (FasL) by malignant cells might be a mechanism for tumor immune escape. We investigated FasL expression by LS 174T colon carcinoma cells. Furthermore, the effects of in vitro stimulation with rIL-2, rIFN-gamma and rTNF-alpha were investigated with regard to a possible regulation of the FasL expression by cytokines. FasL expression was detected by flow cytometry and RT-PCR. We observed a spontaneous expression of FasL by LS 174T cells. Incubation with high-dose rTNF-alpha induced an upregulation of FasL of 23%. rIL-2 and rIFN-gamma did not significantly affect FasL expression. To control whether our cytokine stimulation experiments were suitable to prove an upregulation of membrane proteins by tumor cells, we investigated the expression of ICAM-1, N-CAM, CD44s, CD44v6 and CD44v10. These adhesion molecules were spontaneously expressed by LS 174T cells. Only ICAM-1 and CD44v10 were significantly upregulated by rIFN-gamma and rTNF-alpha, respectively. These results could indicate that cytokines, released by tumor-infiltrating leukocytes, may induce the FasL-dependent apoptotic signal by which tumors downregulate an immunological host response.
Wimmenauer
S
S
Department of General Surgery, University Hospital Freiburg, Germany.
Steiert
A
A
Wolff-Vorbeck
G
G
Xing
B
B
Baier
P K
PK
Rückauer
K D
KD
Kirste
G
G
von Kleist
S
S
D000230:Adenocarcinoma / Q000276:immunology*; D017398:Alternative Splicing; D015703:Antigens, CD / Q000235:genetics; D003110:Colonic Neoplasms / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology*; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma