Senescent Fibroblasts Enhance Early Skin Carcinogenic Events via a Paracrine MMP-PAR-1 Axis

• Published in: PloS one Vol. 8; no. 5; p. e63607
• Main Authors: Malaquin, Nicolas, Vercamer, Chantal, Bouali, Fatima, Martien, Sébastien, Deruy, Emeric, Wernert, Nicolas, Chwastyniak, Maggy, Pinet, Florence, Abbadie, Corinne, Pourtier, Albin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.05.2013; Public Library of Science (PLoS)
• Subjects: Adult; Age; Aging; Analysis; Antibodies; Biology; Blocking antibodies; Breast cancer; Carcinogenesis; Carcinogens; Cell migration; Cell Movement - drug effects; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Cells, Cultured; Cellular Senescence; Compartments; Conditioning; Epithelial-Mesenchymal Transition - genetics; Female; Fibroblasts; Fibroblasts - metabolism; Gelatinase A; Gene Expression; Hepatocyte Growth Factor - pharmacology; Humans; Inflammation; Interstitial collagenase; Keratinocytes; Keratinocytes - metabolism; Life Sciences; Matrix metalloproteinase; Matrix Metalloproteinase 1 - biosynthesis; Matrix Metalloproteinase 2 - biosynthesis; Matrix metalloproteinases; Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; Medicine; Melanoma; Mesenchyme; Metastases; Metastasis; Molecular modelling; Paracrine Communication; Paracrine signalling; Pharmacology; Proteinase-activated receptor 1; Receptor, PAR-1 - genetics; Receptor, PAR-1 - metabolism; Secretion; Secretome; Senescence; siRNA; Skin; Skin - metabolism; Skin - pathology; Skin carcinoma; Transformation; Transformed cells; Transforming Growth Factor beta1 - pharmacology; Tumors; Young Adult; France

The incidence of carcinoma increases greatly with aging, but the cellular and molecular mechanisms underlying this correlation are only partly known. It is established that senescent fibroblasts promote the malignant progression of already-transformed cells through secretion of inflammatory mediator...