EP 1608970 A2 20051228 - CCN3 COMPOSITIONS AND METHODS
Title (en)
CCN3 COMPOSITIONS AND METHODS
Title (de)
CCN3-ZUSAMMENSETZUNGEN UND VERFAHREN
Title (fr)
COMPOSITIONS DE LA CCN3 ET PROCEDES ASSOCIES
Publication
Application
Priority
- US 2004009810 W 20040331
- US 45936103 P 20030331
Abstract (en)
[origin: WO2004090109A2] CCN3 (Nov) is a matricellular protein of the CCN family, which also includes CCN1 (CYR61), CCN2 (CTGF), CCN4 (WISP-1), CCNS (WISP-2), and CCN6 (WISP-3). During development, CCN3 is expressed widely in derivatives of all three germ layers, and high levels of expression is observed in smooth muscle cells of the arterial vessel wall. Altered expression of CCN3 has been observed in a variety of tumors, including hepatocellular carcinomas, Wilm's tumors, Ewing's sarcomas, gliomas, rhabdomyosarcomas, and adrenocortical carcinomas. To understand its biological functions, we have investigated the activities of purified recombinant CCN3. We show that in endothelial cells, CCN3 supports cell adhesion, induces directed cell migration (chemotaxis), and promotes cell survival. Mechanistically, CCN3 supports human umbilical vein endothelial cell adhesion through multiple cell surface receptors, including integrins alphavß3, alpha5ß1, alpha6ß1, and heparan sulfate proteoglycans. In contrast, CCN3-induced cell migration is dependent on integrins alphavß3 and alpha5ß1, whereas alpha6ß1 does not play a role in this process. Although CCN3 does not contain a RGD sequence, it binds directly to immobilized integrins alphavß3 and alpha5ß1 with half maximal binding occurring at 10 nM and 50 nM CCN3, respectively. Furthermore, CCN3 induces neovascularization when implanted in rat cornea, demonstrating that it is a novel angiogenic inducer. Together, these findings show that CCN3 is a ligand of integrins alphavß3 and alpha5ß1, acts directly upon endothelial cells to stimulate pro-angiogenic activities, and induces angiogensis in vivo.
IPC 1-7
IPC 8 full level
A61K 38/04 (2006.01); A61K 49/00 (2006.01); C07K 14/47 (2006.01); C07K 16/18 (2006.01); C07K 16/28 (2006.01); G01N 33/53 (2006.01); G01N 33/68 (2006.01)
IPC 8 main group level
C12N (2006.01)
CPC (source: EP)
C07K 14/47 (2013.01); C07K 16/18 (2013.01); G01N 33/6863 (2013.01); C07K 2317/73 (2013.01); G01N 2333/515 (2013.01)
Designated contracting state (EPC)
AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LI LU MC NL PL PT RO SE SI SK TR
DOCDB simple family (publication)
WO 2004090109 A2 20041021; WO 2004090109 A3 20050721; EP 1608970 A2 20051228; EP 1608970 A4 20060614
DOCDB simple family (application)
US 2004009810 W 20040331; EP 04758632 A 20040331