2. Ερευνητικές δημοσιεύσεις | Research publications

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https://hdl.handle.net/10889/2147
Η συλλογή αυτή συγκεντρώνει τις δημοσιεύσεις του διδακτικού και ερευνητικού προσωπικού του Πανεπιστημίου Πατρών σε επιστημονικά περιοδικά ή σε επιστημονικές εκδηλώσεις (συνέδρια, ημερίδες, κλπ.).

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Browsing 2. Ερευνητικές δημοσιεύσεις | Research publications by Author "Agalioti, Theodora"

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    Open Access
    Mutant KRAS promotes malignant pleural effusion formation
    Agalioti, Theodora; Giannou, Anastasios; Krontira, Anthi; Kanellakis, Nikolaos; Kati, Danai; Vreka, Malamati; Pepe, Mario; Spella, Magda; Lilis, Ioannis; Zazara, Dimitra; Nikolouli, Eirini; Spiropoulou, Nikolitsa; Papadakis, Andreas; Papadia, Konstantina; Voulgaridis, Apostolos; Stamou, Panagiota; Meiners, Silke; Eickelberg, Oliver; Snyder, Linda; Antimisiaris, Sophia; Kardamakis, Dimitrios; Psallidas, Ioannis; Marazioti, Antonia; Stathopoulos, Georgios; Αγαλιώτη, Θεοδώρα; Γιάννου, Αναστάσιος; Κροντηρά, Ανθή; Κανελλάκης, Νικόλαος; Κατή, Δανάη; Βρεκά, Μαλαματή; Σπέλλα, Μάγδα; Λιλής, Ιωάννης; Ζαζάρα, Δήμητρα; Νικολούλη, Ειρήνη; Σπυροπούλου, Νικολίτσα; Παπαδάκης, Ανδρέας; Παπαδιά, Κωνσταντίνα; Βουλγαρίδης, Απόστολος; Χαροκόπος, Βαγγέλης; Στάμου, Παναγιώτα; Αντιμησιάρη, Σοφία; Καρδαμάκης, Δημήτριος; Ψαλλίδας, Ιωάννης; Μαραζιώτη, Αντωνία; Σταθόπουλος, Γεώργιος
    Τμήμα Ιατρικής (Δημοσ. Π.Π. σε περιοδικά)
    Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity. However, the mechanisms responsible for the development of MPE are still obscure. Here we show that mutant KRAS is important for MPE induction in mice. Pleural disseminated, mutant KRAS bearing tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into the bloodstream to mobilize myeloid cells from the host bone marrow to the pleural space via the spleen. These cells promote MPE formation, as indicated by splenectomy and splenocyte restoration experiments. In addition, KRAS mutations are frequently detected in human MPE and cell lines isolated thereof, but are often lost during automated analyses, as indicated by manual versus automated examination of Sanger sequencing traces. Finally, the novel KRAS inhibitor deltarasin and a monoclonal antibody directed against CCL2 are equally effective against an experimental mouse model of MPE, a result that holds promise for future efficient therapies against the human condition.
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    Myeloid-derived interleukin-1β drives oncogenic KRAS-NF-κΒ addiction in malignant pleural effusion
    Marazioti, Antonia; Lilis, Ioannis; Vreka, Malamati; Apostolopoulou, Hara; Kalogeropoulou, Argyro; Giopanou, Ioanna; Giotopoulou, Georgia; Krontira, Anthi; Iliopoulou, Marianthi; Kanellakis, Nikolaos; Agalioti, Theodora; Giannou, Anastasios; Jones-Paris, Celestial; Iwakura, Yoichiro; Kardamakis, Dimitrios; Blackwell, Timothy; Taraviras, Stavros; Spella, Magda; Stathopoulos, Georgios; Μαραζιώτη, Αντωνία; Λιλής, Ιωάννης; Βρεκά, Μαλαματή; Αποστολοπούλου, Χαρά; Καλογεροπούλου, Αργυρώ; Γιοπάνου, Ιωάννα; Γιωτοπούλου, Γεωργία; Κροντηρά, Ανθή; Ηλιοπούλου, Μαριάνθη; Κανελλάκης, Νικόλαος; Αγαλιώτη, Θεοδώρα; Γιάννου, Αναστάσιος; Καρδαμάκης, Δημήτριος; Ταραβήρας, Σταύρος; Σπέλλα, Μάγδα; Σταθόπουλος, Γεώργιος
    Τμήμα Ιατρικής (Δημοσ. Π.Π. σε περιοδικά)
    Malignant pleural effusion (MPE) is a frequent metastatic manifestation of human cancers. While we previously identified KRAS mutations as molecular culprits of MPE formation, the underlying mechanism remained unknown. Here, we determine that non-canonical IKKα-RelB pathway activation of KRAS-mutant tumor cells mediates MPE development and this is fueled by host-provided interleukin IL-1β. Indeed, IKKα is required for the MPE-competence of KRAS-mutant tumor cells by activating non-canonical NF-κB signaling. IL-1β fuels addiction of mutant KRAS to IKKα resulting in increased CXCL1 secretion that fosters MPE-associated inflammation. Importantly, IL-1β-mediated NF-κB induction in KRAS-mutant tumor cells, as well as their resulting MPE-competence, can only be blocked by co-inhibition of both KRAS and IKKα, a strategy that overcomes drug resistance to individual treatments. Hence we show that mutant KRAS facilitates IKKα-mediated responsiveness of tumor cells to host IL-1β, thereby establishing a host-to-tumor signaling circuit that culminates in inflammatory MPE development and drug resistance.
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    NRAS destines tumor cells to the lungs
    Γιάννου, Αναστάσιος; Μαραζιώτη, Αντωνία; Κανελλάκης, Νικόλαος; Γιοπάνου, Ιωάννα; Λίλης, Ιωάννης; Ζαζάρα, Δήμητρα; Νταλιάρδα, Γιαννούλα; Κατή, Δανάη; Αρμένης, Βασίλειος; Γιωτοπουλου, Γεωργία; Κροντηρά, Ανθή; Λιανου, Μαρίνα; Αγαλιώτη, Θεοδώρα; Βρέκα, Μαλαματή; Παπαγεωργοπούλου, Μαρία; Φούζας, Σωτήριος; Καρδαμάκης, Δημήτριος; Ψαλλίδας, Ιωάννης; Σταθόπουλος, Γεώργιος; Σπέλλα, Μάγδα; Giannou, Anastasios; Marazioti, Antonia; Kanellakis, Nikolaos; Giopanou, Ioanna; Lilis, Ioannis; Zazara, Dimitra; Ntaliarda, Giannoula; Kati, Danai; Armenis, Vasileios; Giotopoulou, Georgia; Krontira, Anthi; Lianou, Marina; Agalioti, Theodora; Vreka, Malamati; Papageorgopoulou, Maria; Fouzas, Sotirios; Kardamakis, Dimitrios; Psallidas, Ioannis; Spella, Magda; Stathopoulos, Georgios
    Τμήμα Ιατρικής (Δημοσ. Π.Π. σε περιοδικά)
    The lungs are frequently affected by cancer metastasis. Although NRAS mutations have been associated with metastatic potential, their exact role in lung homing is incompletely understood. We cross-examined the genotype of various tumor cells with their ability for automatic pulmonary dissemination, modulated NRAS expression using RNA interference and NRAS overexpression, identified NRAS signaling partners by microarray, and validated them using Cxcr1- and Cxcr2-deficient mice. Mouse models of spontaneous lung metastasis revealed that mutant or overexpressed NRAS promotes lung colonization by regulating interleukin-8-related chemokine expression, thereby initiating interactions between tumor cells, the pulmonary vasculature, and myeloid cells. Our results support a model where NRAS-mutant, chemokine-expressing circulating tumor cells target the CXCR1-expressing lung vasculature and recruit CXCR2-expressing myeloid cells to initiate metastasis. We further describe a clinically relevant approach to prevent NRAS-driven pulmonary metastasis by inhibiting chemokine signaling. In conclusion, NRAS promotes the colonization of the lungs by various tumor types in mouse models. IL-8-related chemokines, NRAS signaling partners in this process, may constitute an important therapeutic target against pulmonary involvement by cancers of other organs.