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Metaloproteazi MMP-2 in MMP-9 v mikrookolju glioblastoma
ID Banovšek, Nika (Author), ID Breznik, Barbara (Mentor) More about this mentor... This link opens in a new window

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Abstract
Glioblastom je najpogostejši in najagresivnejši primarni možganski tumor centralnega živčnega sistema, ki je zelo invaziven in odporen na klasično zdravljenje z radioterapijo in kemoterapijo. Ključni dejavnik, ki prispeva k ponovitvi tumorja in smrti bolnikov, je sposobnost invazije rakavih celic v okoliško možgansko tkivo. Proteaze so ključni encimi odgovorni za proces invazije rakavih celic. Metaloproteazi 2 in 9 (MMP-2 in -9), ki spadata v skupino želatinaz, sta povezani z visoko malignimi gliomi in napredovanjem tumorja ter sta kritični proteazi za invazijo rakavih celic ter njihovo interakcijo z mikrookoljem tumorja. V diplomski nalogi smo določali izražanje in lokalizacijo MMP-2 in MMP-9 v tumorskih biopsijah in organoidih glioblastoma, ki predstavljajo napreden 3D model, ki vsebuje tumorsko mikrookolje. Uporabili smo metodo imunofluorescence, kjer smo uporabili specifična primarna protitelesa proti pro in aktivni obliki MMP-2/-9 ter označevalcem rakavih in drugih celic mikrookolja tumorja kot so imunske celice. Rezultati so pokazali, da se MMP-2 in MMP-9 enako izražata v tkivu kot v pripadajočih organoidih glioblastoma. Izražata se v imunskih celicah, kakor tudi v tumorskih celicah glioblastoma. Kakšna je njuna vloga v imunskih celicah v tumorskem mikrookolju in ali sta odločilni proteazi pri invaziji glioblastomskih celic v okoliško možganovino so naša nadaljnja raziskovalna vprašanja. Dane ugotovitve bodo pripomogle k boljšemu razumevanju napredovanja glioblastoma in možnosti nadaljnjega ciljanja MMP-2/-9 v glioblastomu in vivo.

Language:Slovenian
Keywords:glioblastom, mikrookolje, MMP-2, MMP-9
Work type:Bachelor thesis/paper
Typology:2.11 - Undergraduate Thesis
Organization:FKKT - Faculty of Chemistry and Chemical Technology
Year:2022
PID:20.500.12556/RUL-139722 This link opens in a new window
COBISS.SI-ID:126629635 This link opens in a new window
Publication date in RUL:06.09.2022
Views:651
Downloads:73
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Secondary language

Language:English
Title:Metalloproteases MMP-2 and MMP-9 in Microenvironment of Glioblastoma
Abstract:
Glioblastoma is one of the most common and most aggressive primary brain tumours of the central nervous system. It is very invasive and resistant to classical treatment with radiotherapy and chemotherapy. A key factor that contributes to tumour reoccurrence and patient’s death is the ability of cancer cells to invade surrounding brain tissue. Metalloproteases 2 and 9 (MMP-2 and 9), which belong to a group of gelatinases, are associated with high tumour grades and tumour progression and are critical proteases for cancer cell invasion and interaction with tumour microenvironment. In this bachelor thesis we determined the expression and localization of MMP-2/-9 in glioblastoma biopsies and organoids, which present an advanced 3D model that includes tumor microenvironment. We used the method of immunofluorescence, where we used specific antibodies against pro- and active form of MMPs and biomarkers of cancer cells and other cells of the tumour microenvironment, such as immune cells. The results showed that the expression of MMP-2/MMP-9 in the tissue and in the tissue derived organoids is the same. Furthermore MMP-2 and MMP-9 were expressed in immune cells as well as in the GBM tumour cells. Our future research questions include what role MMP-2/-9 play in immune cells in the tumor microenvironment and are these proteases crucial in glioblastoma cell invasion into the surrounding brain tissue. These results will lead to a better understanding of glioblastoma progression and the possibility of further targeting of MMP-2/-9 in glioblastoma in vivo.

Keywords:glioblastoma, microenvironment, MMP-2, MMP-9

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