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 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.
Herzberg
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F
Department of Hematology and Oncology, University Medical Center Benjamin Franklin, Free University of Berlin, Germany. herzberg@fub46.zedat.fu-berlin.de.
Schöning
M
M
Schirner
M
M
Topp
M
M
Thiel
E
E
Kreuser
E D
ED
D000818:Animals; D002277:Carcinoma / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005353:Fibronectins; D016023:Integrins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4