JCB logo
Avanti Polar Lipids
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 24 January 2005. doi:10.1083/jcb.200403078
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 3, 489-499
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 4920K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Laurent-Matha, V.
Right arrow Articles by Liaudet-Coopman, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Laurent-Matha, V.
Right arrow Articles by Liaudet-Coopman, E.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Article

 Catalytically inactive human cathepsin D triggers fibroblast invasive growth

Valérie Laurent-Matha1, Sharon Maruani-Herrmann1, Christine Prébois1, Mélanie Beaujouin1, Murielle Glondu1, Agnès Noël2, Marie Luz Alvarez-Gonzalez2, Sylvia Blacher2, Peter Coopman3, Stephen Baghdiguian4, Christine Gilles2, Jadranka Loncarek5, Gilles Freiss1, Françoise Vignon1, and Emmanuelle Liaudet-Coopman1

1 INSERM U540 Endocrinologie Moléculaire et Cellulaire des Cancers, Université de Montpellier 1, 34090 Montpellier, France
2 Laboratory of Tumor and Developmental Biology, University of Liège, Sart-Tilman, B-4000 Liège, Belgium
3 CNRS UMR 5539, Université Montpellier 2, 34095 Montpellier, France
4 CNRS UMR 5554, Université Montpellier 2, 34095 Montpellier, France
5 INSERM EMI 0229, Centre de Recherche en Cancérologie, CRLC Val d'Aurelle-Paul Lamarque, 34298 Montpellier, France

Correspondence to E. Liaudet-Coopman: liaudet{at}montp.inserm.fr

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.

V. Laurent-Matha and S. Maruani-Hermann contributed equally to this work.

Sharon Maruani-Herrmann's present address is Dina Raveh's laboratory, Life Science Dept., Ben Gourion University of the Negev, Beer-Sheva 84105, Israel.

V. Laurent-Matha's present address is Cellular Biology Unit, IGH, CNRS UPR 1142, 34396 Montpellier, Cedex 05, France.

Abbreviations used in this paper: 3D, three-dimensional; cath-D, cathepsin D; HMF, human mammary fibroblast; luc siRNA, luciferase siRNA; Man-6-P, Mannose-6-phosphate.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents