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

Citations of this article
Mendeley users who have this article in their library.


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 proinflammatory 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 α (TNF-α) 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-α abolished contact-mediated inhibition of cell proliferation and stimulated cell growth both in the absence of exogenous mitogens and under anchorage-independent conditions. TNF-α induced the expression of matrix metalloproteinase 9 (MMP-9). Addition of the NMP inhibitor BB-94 abrogated TNF-α-induced 3D scattering. TNF-α also enhanced the attachment of 31EG4-2A4 cells to type-I collagen and markedly increased the expression of the α2 integrin subunit. Addition of a blocking antibody to β1-integrin or of rhodocetin (a specific α2β1 antagonist) to collagen-gel cultures abrogated 3D scattering. Collectively, these results demonstrate an essential role for MMPs and α2β1 integrin in the invasive response of 31EG4-2A4 cells to TNF-α. We propose that the biological activities described in this study contribute to the ability of TNF-α to promote tumour progression and cancer-cell dissemination.




Montesano, R., Soulié, P., Eble, J. A., & Carrozzino, F. (2005). Tumour necrosis factor α confers an invasive, transformed phenotype on mammary epithelial cells. Journal of Cell Science, 118(15), 3487–3500. https://doi.org/10.1242/jcs.02467

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free