INVESTIGADORES
CURINO Alejandro Carlos
congresos y reuniones científicas
Título:
uPARAP/Endo 180-dependent intracellular collagen degradation- a major pathway of pathophysiological collagen turnover.
Autor/es:
BUGGE T.H.; CURINO A. C.; ENGELHOLM L.H.; BOYE S. N.; KJOLLER L.; WAGENAAR-MILLER R.,; MOLINOLO A.A.; BEHRENDT N.
Lugar:
San Diego, CA, USA.
Reunión:
Congreso; Second National Meeting of the American Society for Matrix Biology.; 2004
Institución organizadora:
American Society for Matrix Biology.
Resumen:
uPARAP/Endo180-dependent Intracellular Collagen Degradation - a Major Pathway of Pathophysiological Collagen Turnover.
*Bugge H Thomas, OPCB/NIDCR/NIH, Bethesda, MD, USA; Alejandro C Curino, OPCB/NIDCR/NIH, Bethesda, MD, USA; Engelholm H Lars, Finsen Laboratory, Copenhagen, Denmark; Boye S. Nielsen, Finsen Laboratoy, Copenhagen, Denmark; Kjoller Lars, Finsen Laboratory, Copenhagen, Denmark; Wagenaar-Miller Rcbecca, OPCB/NIDCR/NIH, Bethesda, MD, USA; Molinolo A Alfredo, OPCB/NIDCR/NIH, Bethesda, MD, USA; Behrendt Niels: Finsen Laboratory, Copenhagen, Denmark;
The urokinase plasminogin activator receptor-associated protein (uPARAP)/Endo180 is a recently identified member of the macrophage mannosa receptor family of constitutively recycling endocytic transmembrane glycoproteins. uPARAP/Endol80 is a 180 kDa multidomain glycoprotein that consists of an N-terminal cysteine-rich domain, a collagen binding fibronectin type II domain, eight C-type carbohydrate recognition domains, a transmembrane domain, and a short C terminal cytoplasmic tail. Extensive in situ hybridization and immunohistochemical studies reveal that uPARAPlEndo180 is expressed at low levels in homeostatic tissues. However, the novel receptor is abundantly expressed by mesenchymal cells located at sites of active tissue remodeling and rapid extra cellular matrix turnover, and is co expressed with matrix degrading proteases. This expression pattern includes both physiological tissue remodeling (endochondral and intramembranous ossification) and pathophysiological tissue remodeling (tumor invasion). Surprisingly, genetic ablation of uPARAPIEndo180 leads to a specific and near complete abrogation of the ability of mesenchymal cells to internalize and degrade a range of collagen species. This defect is apparent in both cultured uPARAP/Endol80-deficient fibroblast and in fibroblast-like cells within primary explants of uPARAP/Endol80 deficient Polyoma virus middle T-induced mammary tumors. This novel uPARAP/Endo 180 dependent intracellular collagen degradation pathway is critical to collagen turnover during tumor progression, as evidenced by accumulation of interstitial collagen and impaired growth of Polyoma virus middle T-induced mammary tumors in uPARAP/Endo180-deficient mice. Taken together, these studies identify uPARAP/Endo180-mediated intracellular degradation of collagen as a major pathway for the turnover of this abundant extracellular matrix component within a pathophysiological context.