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IL-4 and TNF-α induce changes in integrin expression and adhesive properties and decrease the lung-colonizing potential of HT-29 colon carcinoma cells

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The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor α (TNF-α) to modify integrin expression and adhesive functions of tumor cells in vitro and to examine corresponding metastatic effects in vivo. Preincubation of HT-29 cells with 100 U/ml of IL-4 for 48 h downregulated the surface expression of the integrin subunits α2, α3, βl and β4 after 48 h, whereas the α1 subunit was upregulated. In contrast, 100 U/ml of TNF-a selectively upmodulated the expression of av. Attachment to fibronectin of cells treated with IL-4 increased twofold (63.5% vs 32.4%). Adhesion to fibronectin (54.0% vs 32.4%) and vitronectin (37.9% vs 16.4%) was elevated in the case of TNF-a stimulation. Using an experimental metastasis model, HT-29 cells showed a significant reduction of their lung-colonizing potential in nude mice when preincubated with IL-4 for 48 h before intravenous injection. The decrease also observed for TNF-α-treated cells was less pronounced. The data indicate that the cytokines IL-4 and TNF-α can act as direct regulators of adhesive mechanisms of tumor cells bearing adequate receptors, thus influencing lung-colony formation.

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Authors and Affiliations

  1. Department of Hematology and Oncology, University Medical Center Benjamin Franklin, Free University of Berlin, Germany

    Frank Herzberg, Michael Schöning, Max Topp, Eckhard Thiel & Ernst-Dietrich Kreuser

  2. Department of Experimental Oncology, Schering AG, Berlin, Germany

    Michael Schirner

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  1. Frank Herzberg
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  2. Michael Schöning
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  3. Michael Schirner
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Correspondence to Frank Herzberg.

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Herzberg, F., Schöning, M., Schirner, M. et al. IL-4 and TNF-α induce changes in integrin expression and adhesive properties and decrease the lung-colonizing potential of HT-29 colon carcinoma cells. Clin Exp Metast 14, 165–175 (1996). https://doi.org/10.1007/BF00121213

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  • DOI: https://doi.org/10.1007/BF00121213

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