Interleukin 4 receptor expression and growth inhibition of gastric carcinoma cells by interleukin 4.
The expression of the interleukin 4 (IL-4) receptor (IL-4R) and effects of human recombinant IL-4 on human gastric carcinoma cell lines were studied. We demonstrated that IL-4 inhibited the growth of gastric carcinoma cells in a dose dependent manner (0.1-100 units/ml) in a [3H]thymidine incorporation proliferation assay. The gastric carcinoma cells varied in sensitivity to treatment with low dose IL-4. Treatment of cells with IL-4 altered the morphology of the cells to a "flattened" morphological shape resembling differentiation. The IL-4-mediated growth inhibition was significantly abrogated by neutralization of IL-4 with specific anti-IL-4 antibody. IL-4R expression on the cell surface was determined by assessing biotin-labeled IL-4 binding to cells using flow cytometry. IL-4R expression ranged from 5 to 85% of total cell population in the gastric carcinoma cell lines assessed. There was a positive correlation between the sensitivity to IL-4-mediated growth inhibition and IL-4R expression. By Northern blot analysis, we demonstrated that mRNA of IL-4R was expressed in the gastric carcinoma cells. Using in situ hybridization, we confirmed that IL-4R mRNA was expressed in the gastric carcinoma cell at the single cell level. By using a sensitive polymerase chain reaction technique, we demonstrated that gastric carcinoma cells expressed IL-4 mRNA, suggesting a possible autocrine loop. These studies indicate that IL-4 can significantly modulate gastric carcinoma cells that possess IL-4R. IL-4R on gastric carcinoma cells may be a potential therapeutic target site for IL-4-directed therapy.
Morisaki
T
T
John Wayne Institute for Cancer Treatment and Research, Santa Monica, California 90404.
Yuzuki
D H
DH
Lin
R T
RT
Foshag
L J
LJ
Morton
D L
DL
Hoon
D S
DS
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000032:analysis* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4