Author/Editor		Magdolen, Ulla; Krol, Janna; Sato, Sumito; Mueller, Markus M; Sperl, Stefan; Krueger, Achim; Schmidt, Manfred; Magdolen, Viktor
Title		Natural inhibitors of tumor-associated proteases
Translated title		Naravni inhibitorji proteaz v tumorju
Type		članek
Source		Radiol Oncol
Vol. and No.		Letnik 36, št. 2
Publication year		2002
Volume		str. 131-43
Language		eng
Abstract		The turnover and remodelling of extracellular matrix (ECM) is an essential part of many normal biological processes including development, morphogenesis, and wound healing. ECM turnover also occurs in severe pathological situations like artherosclerosis, fibrosis, tumor invasion and metastasis. The major proteases involved in this turnover are serine proteases (especially the urokinase-type plasminogen activator/plasmin system), matrix metalloproteases (a family of about 20 zinc-dependent endopeptidases including collagenases, gelatinases, stromelysins, and membrane-type metalloproteases), and cysteine proteases. In vivo, the activity of these proteases is tightly regulated in the extracellular space by zymogen activation and/or controlled inhibition. In the present review, we give an overview on the structure and biochemical properties of important tumor-associated protease inhibitors such as plasminogen activator inhibitor type 1 and type 2 (PAI-1, PAI-2), tissue inhibitors of metalloproteinases (TIMP-1, -2, -3, and -4), and the cysteine protease inhibitor cystatin C. Interestingly, some of these inhibitors of tumor-associated proteases display multiple functions which rather promote than inhibit tumor progression, when the presence of inhibitors in the tumor tissue is not balanced.
Summary		Preoblikovanje zunajceličnega matriksa je osnova mnogih normalnih bioloških procesov, na primer razvoja, morfogeneze in celjenja rane. Preoblikovanje zunajceličnega matriksa opazimo tudi pri zelo resnih patoloških okvarah, na primer pri aterosklerozi, fibrozi, invazivnosti tumorja in razvoju metastaz. V takšno preoblikovanje so najpogosteje vpletene serinske proteaze (še zlasti plazminogenski aktivator-urokinaza / plazminski sistem), metaloproteaze matriksa (družina približno 20 od Zn odvisnih endopeptidaz, vključno s kolagenazami, želatinizami, stromelizini in metaloproteazami membranskega tipa) ter cisteinske proteaze. Dejavnost teh proteaz in vivo v zunajce1ličnem prostoru uravnavata aktiviranje zimogena in nadzorovana inhibicija. V preglednem člahku predstavljamo zgradbo in biokemične lastnosti pomembnih inhibitorjev proteaz, na primer inhibitor plazminogenskega aktivatorja tipa 1 in 2 (PAI-1 in PAI-2,) tkivnih inhibitorjev metaloproteinaz (TIMP-1, -2; -3 in -4) in inhibitorjev cisteinskih proteaz cistatin C, ki so povezani z razvojem tumorja. Zanimivo je, da nekateri od teh inhibitorjev tumorskih proteaz opravljajo hkrati več nalog, ki pravzaprav bolj pospešujejo kot zavirajo napredovanje tumorja, če prisotnost inhibitorjev v tumorskem tkivu ni uravnoteženea.
Descriptors		PLASMINOGEN ACTIVATOR INHIBITOR 1 PLASMINOGEN ACTIVATOR INHIBITOR 2 UROKINASE METALLOPROTEINASES NEOPLASMS CYSTATINS CYSTEINE PROTEINASES