Oncolytic H-1 parvovirus hijacks galectin-1 to enter cancer cells

• Verfasst von: Ferreira, Tiago [VerfasserIn]
• Verfasst von: Kulkarni, Amit [VerfasserIn]
• Verfasst von: Bretscher, Clemens [VerfasserIn]
• Verfasst von: Nazarov, Petr V. [VerfasserIn]
• Verfasst von: Hossain, Jubayer A. [VerfasserIn]
• Verfasst von: Ystaas, Lars A. R. [VerfasserIn]
• Verfasst von: Miletic, Hrvoje [VerfasserIn]
• Verfasst von: Röth, Ralph [VerfasserIn]
• Verfasst von: Niesler, Beate [VerfasserIn]
• Verfasst von: Marchini, Antonio [VerfasserIn]
• Titel: Oncolytic H-1 parvovirus hijacks galectin-1 to enter cancer cells
• Verf.angabe: Tiago Ferreira, Amit Kulkarni, Clemens Bretscher, Petr V. Nazarov, Jubayer A. Hossain, Lars A.R. Ystaas, Hrvoje Miletic, Ralph Röth, Beate Niesler and Antonio Marchini
• E-Jahr: 2022
• Jahr: 11 May 2022
• Umfang: 25 S.
• Fussnoten: Gesehen am 20.07.2022 ; This article belongs to the special issue "Advances in parvovirus research 2022"
• Titel Quelle: Enthalten in: Viruses
• Ort Quelle: Basel : MDPI, 2009
• Jahr Quelle: 2022
• Band/Heft Quelle: 14(2022), 5, special issue, Artikel-ID 1018, Seite 1-25
• ISSN Quelle: 1999-4915
• DOI: doi:10.3390/v14051018
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: galectin-1
• Sach-SW: laminin γ1
• Sach-SW: oncolytic virus immunotherapy
• Sach-SW: protoparvovirus H-1PV
• Sach-SW: virus cell entry
• Sach-SW: virus host interactions
• K10plus-PPN: 1810961718

Abstract

Clinical studies in glioblastoma and pancreatic carcinoma patients strongly support the further development of H-1 protoparvovirus (H-1PV)-based anticancer therapies. The identification of cellular factors involved in the H-1PV life cycle may provide the knowledge to improve H-1PV anticancer potential. Recently, we showed that sialylated laminins mediate H-1PV attachment at the cell membrane. In this study, we revealed that H-1PV also interacts at the cell surface with galectin-1 and uses this glycoprotein to enter cancer cells. Indeed, knockdown/out of LGALS1, the gene encoding galectin-1, strongly decreases the ability of H-1PV to infect and kill cancer cells. This ability is rescued by the re-introduction of LGALS1 into cancer cells. Pre-treatment with lactose, which is able to bind to galectins and modulate their cellular functions, decreased H-1PV infectivity in a dose dependent manner. In silico analysis reveals that LGALS1 is overexpressed in various tumours including glioblastoma and pancreatic carcinoma. We show by immunohistochemistry analysis of 122 glioblastoma biopsies that galectin-1 protein levels vary between tumours, with levels in recurrent glioblastoma higher than those in primary tumours or normal tissues. We also find a direct correlation between LGALS1 transcript levels and H-1PV oncolytic activity in 53 cancer cell lines from different tumour origins. Strikingly, the addition of purified galectin-1 sensitises poorly susceptible GBM cell lines to H-1PV killing activity by rescuing cell entry. Together, these findings demonstrate that galectin-1 is a crucial determinant of the H-1PV life cycle.