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™ 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™ 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 (IC50