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Title

Tumour necrosis factor alpha confers an invasive, transformed phenotype on mammary epithelial cells

Authors
Eble, Johannes A.
Published in Journal of Cell Science. 2005, vol. 118, no. Pt 15, p. 3487-500
Abstract Although loss of cell-cell adhesion and gain of invasive properties play a crucial role in the malignant progression of epithelial tumours, the molecular signals that trigger these processes have not been fully elucidated. In light of the well-established relationship between chronic inflammation and cancer, we hypothesized that pro-inflammatory cytokines disrupt epithelial-cell adhesion and promote cell migration. To test this hypothesis, we used an in vitro model in which 31EG4-2A4 mouse mammary epithelial cells grown in a collagen gel form compact spheroidal colonies. Among the several cytokines examined, tumour necrosis factor alpha (TNF-alpha) caused a pronounced 3D scattering of preformed epithelial-cell colonies and induced 31EG4-2A4 cells grown on top of a collagen gel to invade the underlying matrix. In addition, TNF-alpha abolished contact-mediated inhibition of cell proliferation and stimulated cell growth both in the absence of exogenous mitogens and under anchorage-independent conditions. TNF-alpha induced the expression of matrix metalloproteinase 9 (MMP-9). Addition of the MMP inhibitor BB-94 abrogated TNF-alpha-induced 3D scattering. TNF-alpha also enhanced the attachment of 31EG4-2A4 cells to type-I collagen and markedly increased the expression of the alpha2 integrin subunit. Addition of a blocking antibody to beta1-integrin or of rhodocetin (a specific alpha2beta1 antagonist) to collagen-gel cultures abrogated 3D scattering. Collectively, these results demonstrate an essential role for MMPs and alpha2beta1 integrin in the invasive response of 31EG4-2A4 cells to TNF-alpha. We propose that the biological activities described in this study contribute to the ability of TNF-alpha to promote tumour progression and cancer-cell dissemination.
Keywords AnimalsCell LineCell Movement/drug effectsCell Proliferation/drug effectsCollagen/metabolismEpithelial Cells/cytology/drug effects/metabolismExtracellular Matrix/metabolismIntegrin alpha2beta1/metabolismMammary Glands, Animal/cytology/drug effects/metabolismMetalloproteases/antagonists & inhibitors/metabolismMicePhenotypeProtease Inhibitors/pharmacologyReceptors, Tumor Necrosis Factor, Type I/metabolismTumor Necrosis Factor-alpha/pharmacology
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PMID: 16079290
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MONTESANO, Roberto et al. Tumour necrosis factor alpha confers an invasive, transformed phenotype on mammary epithelial cells. In: Journal of Cell Science, 2005, vol. 118, n° Pt 15, p. 3487-500. https://archive-ouverte.unige.ch/unige:3869

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Deposited on : 2009-10-22

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