Oncolytic H-1 parvovirus hijacks galectin-1 to enter cancer cells
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 potenti...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
11 May 2022
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| In: |
Viruses
Year: 2022, Volume: 14, Issue: 5, Pages: 1-25 |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v14051018 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/v14051018 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1999-4915/14/5/1018 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Gesehen am 20.07.2022 This article belongs to the special issue "Advances in parvovirus research 2022" |
| Physical Description: | Online Resource |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v14051018 |