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Catalytically inactive human cathepsin D triggers fibroblast invasive growth.

ABSTRACT: The aspartyl-protease cathepsin D (cath-D) is overexpressed and hypersecreted by epithelial breast cancer cells and stimulates their proliferation. As tumor epithelial-fibroblast cell interactions are important events in cancer progression, we investigated whether cath-D overexpression affects also fibroblast behavior. We demonstrate a requirement of cath-D for fibroblast invasive growth using a three-dimensional (3D) coculture assay with cancer cells secreting or not pro-cath-D. Ectopic expression of cath-D in cath-D-deficient fibroblasts stimulates 3D outgrowth that is associated with a significant increase in fibroblast proliferation, survival, motility, and invasive capacity, accompanied by activation of the ras-MAPK pathway. Interestingly, all these stimulatory effects on fibroblasts are independent of cath-D proteolytic activity. Finally, we show that pro-cath-D secreted by cancer cells is captured by fibroblasts and partially mimics effects of transfected cath-D. We conclude that cath-D is crucial for fibroblast invasive outgrowth and could act as a key paracrine communicator between cancer and stromal cells, independently of its catalytic activity.

SUBMITTER: Laurent-Matha V

PROVIDER: S-EPMC2171724 | biostudies-literature | 2005 Jan

REPOSITORIES: biostudies-literature

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Catalytically inactive human cathepsin D triggers fibroblast invasive growth.

Laurent-Matha Valérie V Maruani-Herrmann Sharon S Prébois Christine C Beaujouin Mélanie M Glondu Murielle M Noël Agnès A Alvarez-Gonzalez Marie Luz ML Blacher Sylvia S Coopman Peter P Baghdiguian Stephen S Gilles Christine C Loncarek Jadranka J Freiss Gilles G Vignon Françoise F Liaudet-Coopman Emmanuelle E

The Journal of cell biology 20050124 3

The aspartyl-protease cathepsin D (cath-D) is overexpressed and hypersecreted by epithelial breast cancer cells and stimulates their proliferation. As tumor epithelial-fibroblast cell interactions are important events in cancer progression, we investigated whether cath-D overexpression affects also fibroblast behavior. We demonstrate a requirement of cath-D for fibroblast invasive growth using a three-dimensional (3D) coculture assay with cancer cells secreting or not pro-cath-D. Ectopic express ...[more]

PMID: 15668295

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Catalytically inactive human cathepsin D triggers fibroblast invasive growth.

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Catalytically inactive human cathepsin D triggers fibroblast invasive growth.

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