Proteinase-3 directly activates MMP-2 and degrades gelatin and Matrigel; differential inhibition by (-)epigallocatechin-3-gallate.
Proteinase-3 (PR-3), a serine-proteinase mainly expressed by polymorphonuclear leukocytes (PMNs), can degrade a variety of extracellular matrix proteins and may contribute to a number of inflammation-triggered diseases. Here, we show that in addition to Matrigel(TM) components, PR-3 is also able to degrade denatured collagen and directly activate secreted but not membrane-bound pro-MMP-2, a matrix metallo-proteinase instrumental to cellular invasion. In contrast, following addition of purified PR-3 or PMNs to HT1080 tumor cells, dose-dependent inhibition of in vitro Matrigel(TM) invasion is registered. (-)Epigallocatechin-3-gallate (EGCG), the main flavanol in green tea and known to inhibit inflammation and tumor invasion, exerts dose-dependent inhibition of degradation of gelatin (IC(50)<20 micro M) and casein, which is directly triggered by PR-3. The presence of EGCG does not modify the colocalization of MMP-2 and exogenous PR-3 at the cell surface and does not restrain secreted pro-MMP-2 and pro-MMP-9 activation or degradation of a specific, synthetic peptide by PR-3. These results add new activities to the list of those exerted by PR-3 and indicate a differential inhibition as a result of EGCG.
Pezzato
Elga
E
Department of Experimental Biomedical Sciences, Medical School, Padova, Italy.
Donà
Massimo
M
Sartor
Luigi
L
Dell'Aica
Isabella
I
Benelli
Roberto
R
Albini
Adriana
A
Garbisa
Spiridione
S
D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000378:metabolism*; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D053146:Myeloblastin; D009361:Neoplasm Invasiveness; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004338:Drug Combinations; D007797:Laminin; D011480:Protease Inhibitors; D011509:Proteoglycans; C059485:matrigel; D002392:Catechin; D005780:Gelatin; D003094:Collagen; C045651:epigallocatechin gallate; D012697:Serine Endopeptidases; D053146:Myeloblastin; D020778:Matrix Metalloproteinase 2