Reference : ADAMTS-1 metalloproteinase induces a stromal reaction and propotes tumor development ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/8031
ADAMTS-1 metalloproteinase induces a stromal reaction and propotes tumor development in mice.
English
Rocks, Natacha mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Paulissen, Geneviève mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Quesada Calvo, Florence mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques >]
Alvarez Gonzalez, Maria-Luz mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Guéders, Maud mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Hacha, Jonathan mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Gilles, Christine mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement >]
Foidart, Jean-Michel mailto [Université de Liège - ULg > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Cataldo, Didier mailto [Université de Liège - ULg > Département des sciences cliniques > Labo de biologie des tumeurs et du développement - Département des sciences biomédicales et précliniques >]
2008
Cancer Research
American Association for Cancer Research, Inc. (AACR)
68
22
9541-50
Yes (verified by ORBi)
International
0008-5472
1538-7445
Baltimore
MD
[en] ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin motifs), the first described member of the ADAMTS family, is differentially expressed in various tumors. However, its exact role in tumor development and progression is still unclear. The aim of this study was to investigate the effects of ADAMTS-1 transfection in a bronchial epithelial tumor cell line (BZR) and its potential to modulate tumor development. ADAMTS-1 overexpression did not affect in vitro cell properties such as (a) proliferation in two-dimensional culture, (b) proliferation in three-dimensional culture, (c) anchorageindependent growth in soft agar, (d) cell migration and invasion in modified Boyden chamber assay, (e) angiogenesis in the aortic ring assay, and (f) cell apoptosis. In contrast, ADAMTS-1 stable transfection in BZR cells accelerated the in vivo tumor growth after s.c. injection into severe combined immunodeficient mice. It also promoted a stromal reaction characterized by myofibroblast infiltration and excessive matrix deposition. These features are, however, not observed in tumors derived from cells overexpressing a catalytically inactive mutant of ADAMTS-1. Conditioned media from ADAMTS-1–overexpressing cells display a potent chemotactic activity toward fibroblasts. ADAMTS-1 overexpression in tumors was associated with increased production of matrix metalloproteinase-13, fibronectin, transforming growth factor B (TGF-B), and interleukin-1B (IL-1B). Neutralizing antibodies against TGF-B and IL-1B blocked the chemotactic effect of medium conditioned by ADAMTS-1–expressing cells on fibroblasts, showing the contribution of these factors in ADAMTS-1–induced stromal reaction. In conclusion, we propose a new paradigm for catalytically active ADAMTS-1 contribution to tumor development, which consists of the recruitment of fibroblasts involved in tumor growth and tumor-associated stroma remodeling.
Giga-Cancer
http://hdl.handle.net/2268/8031
Agnès NOEL and Didier CATALDO are both senior authors.

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