Inhibition of proliferation and clonal growth of human breast cancer cells by interleukin 13.
We tested the influence of recombinant human interleukin (rhIL)-l3 and rhIL-4 on clonal growth of human breast cancer cell lines. rhIL-13 and rhIL-4 inhibited clonal growth of three of nine lines to approximately 50% of controls (ED50, 0.5 ng/ml). rhIl-13 reduced [3H]thymidine incorporation in all three cell lines: two showing a minor (84% and 83% of controls) and one showing a major response (25% of control). Both cytokines markedly reduced serum-induced G(0/1) exit (approximately 25% versus 60%). 125I-labeled interleukin (IL) 13 binding assays revealed high-affinity binding sites for IL-13 on two of the three responding cell lines (KD approximately 60 pM). (Y124D)IL-4 effectively antagonized all effects of rhIl-13 and rhIL-4, arguing for shared receptor components between them. However, neither rhIl-4 nor (Y124D) IL-4 could displace 125I-labeled IL-13 from binding, although unlabeled rhIL-13 effectively did so. Using reverse transcription-PCR, we studied the expression of the common gamma chain (gammac) in responding cell lines, putatively being shared between IL-4 receptor and IL-13 receptor; none of the three cell lines express gammac. In conclusion, we demonstrate antiproliferative effects of IL-4 and IL-13 on carcinoma cells which express IL-13 binding sites without participation of gammac.
Serve
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Department of Hematology and Oncology, Universitaetsklinikum Benjamin Franklin, Freie Universitaet, Hindenburgdamm, Berlin, Germany.
Oelmann
E
E
Herweg
A
A
Oberberg
D
D
Serve
S
S
Reufi
B
B
Mücke
C
C
Minty
A
A
Thiel
E
E
Berdel
W E
WE
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism / Q000494:pharmacology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D018123:Receptors, Interleukin / Q000378:metabolism; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D007457:Iodine Radioisotopes; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D015847:Interleukin-4