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.

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