The role of the urokinase receptor in extracellular matrix degradation by ht29 human colon carcinoma cells

✍ Scribed by Lars S. Reiter; Egbert K. O. Kruithof; Jean-Francois Cajot; Bernard Sordat

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: French
• Weight: 894 KB
• Volume: 53
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910530316

✦ Synopsis

Urokinase (u-PA) and the urokinase receptor (u-PAR), are thought to play a critical role in the invasive and metastatic properties of cancer cells. The HT29 human colon-carcinoma cell line was selected to evaluate these aspects. HT29 cells express u-PA receptors (100,000 sitedcell, K, = I .5 nM), but no PA activity and therefore are unable to generate plasmin in the presence of plasminogen. These cells have been transfected with a human u-PA cDNA to investigate whether secreted U-PA would enhance in vitro extracellular matrix degradation, and whether the binding of u-PA to the cell surface is determinant. Five clones were selected for stable expression of high PA activity. These clones were capable of marked plasrninogendependent degradation of R22 smooth-muscle-cell-derived extracellular matrix, whereas the parental cell line contributed to an insignificant breakdown only. Aprotinin, polyclonal anti-u-PA IgG, recombinant PAI-2, and co-culture with human PAI-Iproducing mouse L cells significantly inhibited this degradation. Furthermore, a peptide displacing U-PA from its receptor as well as 2 different polyclonal anti-u-PA receptor lgGs decreased the breakdown after 24 hr by as much as 70% and 81%, respectively. These results show that the binding of U-PA to its receptor plays an important role in in vitro matrix breakdown by HT29 U-PA transfectants.