dc.contributor.author | Ferreira, Tiago | |
dc.contributor.author | Kulkarni, Amit | |
dc.contributor.author | Bretscher, Clemens | |
dc.contributor.author | Nazarov, Petr V. | |
dc.contributor.author | Hossain, Md Jubayer al | |
dc.contributor.author | Ystaas, Lars Andreas Rømo | |
dc.contributor.author | Miletic, Hrvoje | |
dc.contributor.author | Röth, Ralph | |
dc.contributor.author | Niesler, Beate | |
dc.contributor.author | Marchini, Antonio | |
dc.date.accessioned | 2023-03-13T12:42:00Z | |
dc.date.available | 2023-03-13T12:42:00Z | |
dc.date.created | 2022-08-25T14:29:01Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 1999-4915 | |
dc.identifier.uri | https://hdl.handle.net/11250/3057958 | |
dc.description.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. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | MDPI | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | Oncolytic H-1 Parvovirus Hijacks Galectin-1 to Enter Cancer Cells | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2022 The Author(s) | en_US |
dc.source.articlenumber | 1018 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.doi | 10.3390/v14051018 | |
dc.identifier.cristin | 2046092 | |
dc.source.journal | Viruses | en_US |
dc.identifier.citation | Viruses. 2022, 14 (5), 1018. | en_US |
dc.source.volume | 14 | en_US |
dc.source.issue | 5 | en_US |