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First published online January 26, 2005

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Ageing fibroblasts cultivate cancer

Cell senescence suppresses cancer by arresting cells that might otherwise become malignant. However, senescent stromal fibroblasts also secrete molecules that, by disrupting the local microenvironment, transform premalignant epithelial cells into tumours. Judith Campisi and colleagues have been examining this antagonistic pleiotropy by studying the effect of senescent fibroblasts on mammary epithelial cell differentiation (see p. 485). They show that premalignant mouse mammary epithelial cells co-injected into mice with senescent human fibroblasts lose their differentiated properties and become malignant. Then, by using 3D co-culture assays that closely mimic physiological conditions, the authors show that senescent human or mouse fibroblasts disrupt the alveolar morphogenesis, functional differentiation and branching morphogenesis of non-malignant breast epithelial cells. Finally, they identify matrix metalloproteinase 3 as the major factor responsible for the effect of senescent fibroblasts on branching morphogenesis. The authors conclude that the alteration of epithelial differentiation by senescent fibroblasts may contribute to cancer and other age-related pathologies and may explain the general loss of tissue function and organization in ageing organisms.

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Related articles in JCS:

Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation

Simona Parrinello, Jean-Philippe Coppe, Ana Krtolica, and Judith Campisi
JCS 2005 118: 485-496. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?