Ekspresija i lokalizacija gasdermina D u sporadičnom karcinomu debelog crijeva

master's thesis

• Title (english): Expression and localization of gasdermin D in sporadic colon cancer
• Author: Petra Pavić
• Mentor: Sonja Marinović (mentor)
• Mentor: Inga Urlić (komentor)
• Committee member: Inga Urlić (predsjednik povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Dunja Leljak-Levanić (član povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2024-10-28, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Karcinom debelog crijeva (engl. colorectal cancer, CRC) treći je najčešće dijagnosticirani karcinom i drugi vodeći uzrok smrtnosti povezane s rakom u svijetu. Njegov razvoj povezan je s nakupljanjem mutacija u onkogenima i tumor-supresorskim genima te promjenama u mikrookolišu, gdje ključnu ulogu imaju imunosne stanice. U crijevima, makrofagi i druge imunosne stanice održavanju homeostazu, ali mogu i potaknuti tumorigenezu kroz kroničnu upalu. Piroptoza je oblik proupalne programirane stanične smrti, posredovan gasderminom D (GSDMD). Aktivacija GSDMD dovodi do formiranja pora na staničnoj membrani što omogućuje oslobađanje staničnog sadržaja i proupalnih citokina čime se pokreće snažan upalni odgovor. Iako je uloga piroptoze u infekciji dobro istražena, malo se zna o ulozi GSDMD u normalnoj sluznici debelog crijeva te njegovoj potencijalnoj ulozi u razvoju CRC-a. U ovom istraživanju analizirali smo ekspresiju i lokalizaciju GSDMD i njegovog pocijepanog oblika u uzorcima sporadičnog CRC-a i pridruženog normalnog tkiva. Rezultati su pokazali postupan pad ekspresije GSDMD u normalnom tkivu sa smanjenjem udaljenost od tumora te gotovo potpunim izostankom u tumorima. U pridruženoj normalnoj sluznici pocijepani oblik GSDMD bio je prisutan u apikalnom dijelu enterocita, vrčastim stanicama epitela i stromi, dok je u uzorcima tumora bio prisutan samo u okolnoj stromi. Ispitivanjem podudarnosti ekspresije GSDMD u stromi s biljezima za makrofage potvrđena je preklapajuća lokalizacija.

Abstract (english)

Colon cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related death worldwide. Its development is linked to accumulation of mutations in oncogenes and tumor suppressor genes, along with changes in the microenvironment, where immune cells play a crucial role. In the intestines, macrophages and other immune cells maintain homeostasis but can also promote tumorigenesis through chronic inflammation. Pyroptosis is a form of pro-inflammatory programmed cell death mediated by gasdermin D (GSDMD). The activation of GSDMD leads to the formation of pores in the cell membrane, allowing the release of cellular contents and pro-inflammatory cytokines, thereby triggering a strong inflammatory response. While the role of pyroptosis in infection is well studied, little is known about the role of GSDMD in the normal colonic mucosa and its potential role in CRC development. In this study, we analyzed the expression and localization of GSDMD and its cleaved form in samples of sporadic CRC and associated normal tissue. The results showed a gradual decrease in GSDMD expression in normal tissue as the distance from the tumor decreased, with almost complete absence in tumors. In the associated normal mucosa, the cleaved form of GSDMD was present in the apical part of enterocytes, goblet cells and in the stroma, while in tumor samples it was only found in the surrounding stroma. The overlap of GSDMD expression in the stroma with macrophage markers confirmed the co-localization.

• Keywords: piroptoza; makrofagi; kolorektalni karcinom; imunohistokemija
• Keywords (english): pyroptosis; macrophages; colorectal cancer; immunohistochemistry
• Language: croatian
• URN:NBN: urn:nbn:hr:217:467514
• Project: Number: HRZZ-IP-2016-06-1430; Title: Mikrosatelitna nestabilnost (MSI i EMAST) u molekularnom profiliranju sporadičnih karcinoma debelog crijeva; Title: Microsatellite instability (MSI and EMAST) in molecular profiling of sporadic colon cancers; Acronym: MSIandEMASTinCRC; Jurisdiction: Croatia; Funder: Hrvatska zaklada za znanost; Funding stream: Research Projects
• Study programme: Title: Molecular Biology-University graduate programme; Study programme type: university; Study level: graduate; Academic / professional title: sveučilišni/a magistar/magistra molekularne biologije (sveučilišni/a magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2025-02-24 13:54:43