Regulation of the urokinase-type plasminogen activator system in mammalian cell lines

master's thesis

• Title (english): Regulacija sustava urokinaznog plazminogenskog aktivatora u staničnim linijama sisavaca
• Author: Laura Marinić
• Mentor: Maja Matulić (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Chemistry and Biochemistry); (Laboratory for Biochemistry); Zagreb
• Defense date and country: 2020-09-21, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

The urokinase-type plasminogen activator system consists of urokinase plasminogen activator (uPA), urokinase type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1). The main role of urokinase is the conversion of plasminogen to plasmin, extracellular protease involved in the degradation of extracellular matrix. uPA system has a role in number of physiological processes, as well as in the metastatic processes. The aim of the study was to compare the urokinase activity and its regulation in different cell lines, under basal conditions and after treatment with several chemotherapeutical agents. Glioblastoma A1235 cells increased the uPA activity after treatment with alkylating agent, retinoic acid and sodium salicylate. Breast cancer cells MDA-MB-231 downregulated urokinase activity after sodium salicylate treatment and increased after treatment with retinoic acid, as well as fibroblast cell line. Dynamin inhibitor inhibited the urokinase activity of A1235 and MDA-MB-231 cells. HEK-293 cells did not change uPA activity after different treatments. In conclusion, the uPA system mechanisms and its regulation are cell-type specific.

Abstract (croatian)

Sustav urokinaznoga plazminogenskoga aktivatora sastoji se od urokinaznog plazminogenskog aktivatora (uPA), receptora urokinaznog plazminogenskog aktivatora (uPAR) i inhibitora plazminogenskog aktivatora-1 (PAI-1). Glavna uloga urokinaze je pretvorba plazminogena u plazmin, izvanstanične proteaze uključene u razgradnju izvanstaničnog matriksa. Uz niz fizioloških procesa, uPA sustav djeluje i kao regulator mikro-okruženja tumora te je uključen u procese metastaziranja. Cilj rada bio je usporediti aktivnost urokinaze i njezinu regulaciju u različitim staničnim linijama, pod bazalnim uvjetima i nakon tretmana s nekoliko kemoterapeutika. Stanice glioblastoma A1235 povećale su aktivnost uPA nakon tretmana alkilirajućim agensom, retinoičnom kiselinom i natrijevim salicilatom. Stanice karcinoma dojke MDA-MB-231 smanjile su aktivnost urokinaze nakon tretmana natrijevim salicilatom, a povećale nakon tretmana retinoičnom kiselinom, kao i stanična linija fibroblasta. Inhibitor dinamina inhibirao je urokinaznu aktivnost stanica A1235 i MDA-MB-231. HEK 293 stanice nisu promijenile uPA aktivnost nakon različitih tretmana. Zaključno, mehanizmi uPA sustava i njegova regulacija stanično su specifični.

• Keywords: urokinase; plasminogen activator inhibitor-1; dynamin inhibitor; mammalian cell lines; regulation
• Keywords (english): urokinaza; inhibitor plazminogenskog aktivatora-1; inhibitor dinamina; stanične linije sisavaca; regulacija
• Language: english
• URN:NBN: urn:nbn:hr:159:592804
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-01-21 10:34:47