Unit:
Specialty Molecular Biomedicine Mechanisms of Disease, Molecular and Cellular Therapies, and BioinnovationLibrary of the School of Health Sciences
Supervisors info:
Βασιλική Κωστούρου, Ερευνήτρια Β, ΕΚΕΒΕ Α. Φλέμιγκ (Επιβλέπων)
Αριστείδης Ηλιόπουλος, Καθηγητής Ιατρικής Σχολής, ΕΚΠΑ
Αντιγόνη Δήμα, Ερευνήτρια Γ, ΕΚΕΒΕ Α. Φλέμιγκ
Original Title:
Integrin-mediated adhesion in tumour vasculature
Translated title:
Integrin-mediated adhesion in tumour vasculature
Summary:
Beyond the conventional perception of solid tumours as mere masses of cancer cells, advanced cancer research focuses on the complex contributions of tumour-associated host cells that are known as “tumour microenvironment”. Established regulators of cancer progression are the endothelial cells (ECs) comprising the angiogenic tumour vasculature. The integrin-related signalling has a profound influence on multiple aspects of tumour growth including vessel formation, yet the effects of altered expression of integrin mediators remain unclear. PINCH is considered as a crucial adaptor protein of integrin-dependent signalling. Two members of the PINCH protein family (PINCH1 and PINCH2) have been identified and are expressed in a variety of mammalian tissues. Here, we aim to address the impact of PINCH1 on tumour-associated neovasculature. In particular, we applied a comprehensive approach to investigate the lack of PINCH1 expression on murine endothelium in syngeneic tumour models (lung adenocarcinoma or melanoma-induced subcutaneous tumours). EC-specific PINCH1 ablation led to decreased growth of lung adenocarcinoma but not melanoma tumours. Attenuated tumour progression was accompanied by decreased vessel leakage in knockout (KO) tumours compared to control. To address potential biological compensation, we confirmed PINCH2 expression by ECs and generated double PINCH KO tumour-bearing mice. Complete PINCH ablation from ECs resulted in reduced volume and is likely to affect the vessel density of lung adenocarcinoma-derived tumours. Together, our work offers valuable insight into the role of PINCH1 and PINCH2 on cancer biology using in vivo tumour model approaches and imaging technology.
Based on recent findings in the lab, the second aim of this study was to explore the presence of local RNA translation on integrin-related structures (termed as focal adhesions or FAs) of ECs. After extensive protocol modifications and standardization, we managed to isolate sufficient amounts of high-quality RNA from EC FAs, supporting the FA-localized translation hypothesis.
Main subject category:
Health Sciences
Keywords:
Integrin signalling, Tumour angiogenesis, Endothelial cells, PINCH, Focal adhesions, RNA translation
Number of references:
188
