Growth inhibition of human colorectal-carcinoma cells by interleukin-4 and expression of functional interleukin-4 receptors.
The growth-inhibitory effect of interleukin-4 (IL-4) was investigated in a panel of 7 human colorectal-carcinoma cell lines. In 5 cell lines (HT29, WiDr, LS411N, LS513, LS1034) a dose-dependent reduction of proliferation was documented. At 100 U/ml, IL-4 inhibited thymidine incorporation between 45 and 75% and MTT conversion (26 to 41%). The ability of LS513 and WiDr cells to form colonies after IL-4 treatment was reduced by 85 and 62% respectively. LS513 was the most sensitive cell line, with IL-4 inducing half-maximal inhibition at 5 to 6 U/ml. The inhibitory effect of IL-4 was completely neutralized by anti-IL-4 antibodies. Northern-blot analysis revealed the presence of IL-4-receptor (IL-4R) mRNA in all cell lines. The membrane expression of the 130-kDa IL-4R was assessed by FACS, utilizing an anti-IL-4R monoclonal antibody and was confirmed by biotinylated IL-4 binding. Our results attribute an important role for IL-4 as a negative regulator of colorectal-carcinoma cell growth, thus indicating a possible avenue for intervention in this disease.
Lahm
H
H
Department of Cellular Biology, Swiss Institute for Experimental Cancer Research, Epalinges.
Schnyder
B
B
Wyniger
J
J
Borbenyi
Z
Z
Yilmaz
A
A
Car
B D
BD
Fischer
J R
JR
Givel
J C
JC
Ryffel
B
B
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D019948:Receptors, Interleukin-4; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4