Study of the role of osteopontin in immune response in the tumour microenvironment

Postgraduate Thesis uoadl:2967244 105 Read counter

Unit:
Κατεύθυνση Εφαρμογές της Βιολογίας στην Ιατρική
Library of the School of Science
Deposit date:
2021-11-24
Year:
2021
Author:
Filika Maria
Supervisors info:
Ουρανία Τσιτσιλώνη, Καθηγήτρια Ανοσολογίας, Τμήμα Βιολογίας, ΕΚΠΑ
Δημήτριος Ι. Στραβοπόδης, Αναπληρωτής Καθηγητής Βιολογίας Κυττάρου & Ανάπτυξης, Τμήμα Βιολογίας, ΕΚΠΑ
Παναγιώτα Παπαζαφείρη, Αναπληρώτρια Καθηγήτρια Φυσιολογίας Ζώων, Τμήμα Βιολογίας, ΕΚΠΑ
Original Title:
Μελέτη του ρόλου της οστεοποντίνης στην ανοσολογική αντίδραση στο μικροπεριβάλλον του όγκου
Languages:
Greek
Translated title:
Study of the role of osteopontin in immune response in the tumour microenvironment
Summary:
Osteopontin (OPN) is a non-collagenous extracellular matrix glycoprotein, which is expressed by a broad range of cells and is involved in a variety of cellular processes, such as migration and cell adhesion, due to its ability to interact with cells through its receptors integrins and CD44. It has been shown that OPN is highly expressed in activated CD4+ immune cells and participates in the regulation of immune responses. OPN is also a protein produced by many cancers and is actively involved in tumour progression through processes such as angiogenesis and metastasis. Recently, the great contribution of the tumour microenvironment in cancer progression and promotion of metastasis is increasingly appreciated. The two-way communication between cancer cells and tumour microenvironment strongly influences the onset and progression of the disease, as well as the prognosis of the patient. Tumor-derived OPN appears to have a significant effect on the tumour microenvironment, regulating the immune response. The aim of this project is to study the role of tumour OPN in the regulation of immune response in the tumor microenvironment. For this reason, the reduction of OPN expression was initially achieved, using shRNA technology, in the B16F10 melanoma cell line. Then, wild type B16F10 and B16F10 shRNA-OPN were used to induce melanoma in C57BL/6 Foxp3/GFP mice. This was followed by the analysis of the cell populations of the tumors using flow cytometry, as well as the measurement of their size. The results showed that B16F10 cells that received the shRNA oligonucleotides, actually expressed reduced OPN, compared to wild type B16F10 cells. In addition, the incorporation of these oligonucleotides had no impact on cell viability. The decrease in OPN expression resulted in a decrease in the percentage, and possibly in the function of Foxp3 + cells in the tumor microenvironment of mice, as well as an increase in the percentage of CD4 + and CD8 + cells. In addition, mice with melanoma expressing reduced OPN formed smaller tumors compared to mice with B16F10 melanoma.
Main subject category:
Science
Keywords:
osteopontin (OPN), tumour microenvironment, immune response, induced melanoma, melanoma cell line B16F10, shRNA-OPN, T regulatory cells (Treg).
Index:
Yes
Number of index pages:
2
Contains images:
Yes
Number of references:
25
Number of pages:
70
Μελέτη του ρόλου της OPN στην ανοσολογική αντίδραση στο μικροπεριβάλλον του όγκου.pdf (2 MB) Open in new window