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

The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) 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...

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Bibliographic Details
Published in:Clinical & experimental metastasis 1996-03, Vol.14 (2), p.165-175
Main Authors: Herzberg, F, Schöning, M, Schirner, M, Topp, M, Thiel, E, Kreuser, E D
Format: Article
Language:English
Subjects:
Animals
Carcinoma - pathology
Cell Adhesion - drug effects
Cell Division - drug effects
Colonic Neoplasms - pathology
Female
Fibronectins - metabolism
Gene Expression
Humans
Integrins - genetics
Integrins - metabolism
Interleukin-4 - pharmacology
Lung Neoplasms - secondary
Mice
Mice, Nude
RNA, Messenger - genetics
RNA, Neoplasm - genetics
Tumor Necrosis Factor-alpha - pharmacology
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Summary:The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) 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 alpha 2, alpha 3, beta 1 and beta 4 after 48 h, whereas the alpha 1 subunit was upregulated. In contrast, 100 U/ml to TNF-alpha selectively upmodulated the expression of alpha v. 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-alpha 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-alpha-treated cells was less pronounced. The data indicate that the cytokines IL-4 and TNF-alpha can act as direct regulators of adhesive mechanisms of tumor cells bearing adequate receptors, thus influencing lung-colony formation.
ISSN:0262-0898
DOI:10.1007/BF00121213