Plasminogen activator and matrix metalloproteinase production and extracellular matrix degradation by rat prostate cancer cells in vitro: correlation with metastatic behavior in vivo.
BACKGROUND
The plasminogen activation (PA) and metalloproteinase (MMP) system are involved in tumor cell migration and invasion.


METHODS
The proteolytic activity of cell lines originating from the rat Dunning R-3327 prostate tumor was analyzed by measuring in vitro extracellular matrix degradation, enzyme activity, and mRNA levels of enzymes, inhibitors, and receptors, and compared with their known metastatic behavior in vivo.


RESULTS
Only the highly metastatic sublines AT-3, MATLu, and MATLyLu showed a high extracellular matrix degradation mediated by urokinase-type plasminogen activator (u-PA). Relatively high levels of u-PA were present in the aggressive cell lines. u-PA receptor mRNA was produced in all cells, and all but AT-1 produced LDL-receptor-related-protein (LRP) mRNA. t-PA mRNA was only found in HIF and MATLu. In gelatin, zymography lysis was observed at 72 kD and 74-76 kD in MATLu and MATLyLu cells, respectively. MMP-2 mRNA was present in all cell lines except AT-1 and AT-2, and MMP-3 mRNA was present in AT-2, AT-3, and MATLu.


CONCLUSIONS
These in vitro experiments show that in different rat prostate cancer sublines, proteolytic activity and u-PA-mediated extracellular matrix degradation correlate with their known metastatic behavior in vivo.
Quax
P H
PH
Gaubius Laboratory TNO-PG, Leiden, The Netherlands. PHA.Quax@pg.tno.nl
de Bart
A C
AC
Schalken
J A
JA
Verheijen
J H
JH
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005109:Extracellular Matrix / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D066298:In Vitro Techniques; D008297:Male; D008666:Metalloendopeptidases / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009362:Neoplasm Metastasis / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D010960:Plasminogen Activators / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D011467:Prostate / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000032:analysis / Q000235:genetics; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000235:genetics / Q000378:metabolism
D018076:DNA, Complementary; D017395:Plasminogen Activator Inhibitor 1; C524900:Plaur protein, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D008666:Metalloendopeptidases