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Immunohistochemical Characterization and Sensitivity to Human Adenovirus Serotypes 3, 5, and 11p of New Cell Lines Derived from Human Diffuse Grade II to IV Gliomas
Univ Eastern Finland, AI Virtanen Inst Mol Sci, Biotechnol & Mol Med, Kuopio, Finland..ORCID iD: 0000-0002-2816-9874
Kuopio Univ Hosp, NeuroCtr, Kuopio, Finland.;Univ Eastern Finland, Inst Clin Med, Neurosurg, Kuopio, Finland..
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Univ Eastern Finland, Inst Clin Med, Pathol, Kuopio, Finland.;Kuopio Univ Hosp, Dept Pathol, Kuopio, Finland..
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2017 (English)In: Translational Oncology, ISSN 1944-7124, E-ISSN 1936-5233, Vol. 10, no 5, p. 772-779Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Oncolytic adenoviruses show promise in targeting gliomas because they do not replicate in normal brain cells. However, clinical responses occur only in a subset of patients. One explanation could be the heterogenic expression level of virus receptors. Another contributing factor could be variable activity of tumor antiviral defenses in different glioma subtypes.

METHODS:

We established a collection of primary low-passage cell lines from different glioma subtypes (3 glioblastomas, 3 oligoastrocytomas, and 2 oligodendrogliomas) and assessed them for receptor expression and sensitivity to human adenovirus (HAd) serotypes 3, 5, and 11p. To gauge the impact of antiviral defenses, we also compared the infectivity of the oncolytic adenoviruses in interferon (IFN)-pretreated cells with IFN-sensitive Semliki Forest virus (SFV).

RESULTS:

Immunostaining revealed generally low expression of HAd5 receptor CAR in both primary tumors and derived cell lines. HAd11p receptor CD46 levels were maintained at moderate levels in both primary tumor samples and derived cell lines. HAd3 receptor DSG-2 was reduced in the cell lines compared to the tumors. Yet, at equal multiplicities of infection, the oncolytic potency of HAd5 in vitro in tumor-derived cells was comparable to HAd11p, whereas HAd3 lysed fewer cells than either of the other two HAd serotypes in 72 hours. IFN blocked replication of SFV, while HAds were rather unaffected.

CONCLUSIONS:

Adenovirus receptor levels on glioma-derived cell lines did not correlate with infection efficacy and may not be a relevant indicator of clinical oncolytic potency. Adenovirus receptor analysis should be preferentially performed on biopsies obtained perioperatively.

Place, publisher, year, edition, pages
2017. Vol. 10, no 5, p. 772-779
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:uu:diva-336297DOI: 10.1016/j.tranon.2017.07.002ISI: 000411278400009PubMedID: 28797937OAI: oai:DiVA.org:uu-336297DiVA, id: diva2:1176847
Available from: 2018-01-23 Created: 2018-01-23 Last updated: 2018-01-23Bibliographically approved

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Martikainen, Miika

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