Evidence for differential viral oncolytic efficacy in an in vitro model of epithelial ovarian cancer metastasis

Jessica G. Tong, Yudith Ramos Valdes, John W. Barrett, John C. Bell, David Stojdl, Douglas McFadden, J. Andrea McCart, Gabriel E. DiMattia, Trevor G. Shepherd

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Epithelial ovarian cancer is unique among most carcinomas in that metastasis occurs by direct dissemination of malignant cells traversing throughout the intraperitoneal fluid. Accordingly, we test new therapeutic strategies using an in vitro three-dimensional spheroid suspension culture model that mimics key steps of this metastatic process. In the present study, we sought to uncover the differential oncolytic efficacy among three different viruses-Myxoma virus, double-deleted vaccinia virus, and Maraba virus-using three ovarian cancer cell lines in our metastasis model system. Herein, we demonstrate that Maraba virus effectively infects, replicates, and kills epithelial ovarian cancer (EOC) cells in proliferating adherent cells and with slightly slower kinetics in tumor spheroids. Myxoma virus and vaccinia viruses infect and kill adherent cells to a much lesser extent than Maraba virus, and their oncolytic potential is almost completely attenuated in spheroids. Myxoma virus and vaccinia are able to infect and spread throughout spheroids, but are blocked in the final stages of the lytic cycle, and oncolytic-mediated cell killing is reactivated upon spheroid reattachment. Alternatively, Maraba virus has a remarkably reduced ability to initially enter spheroid cells, yet rapidly infects and spreads throughout spheroids generating significant cell killing effects. We show that low-density lipoprotein receptor expression in ovarian cancer spheroids is reduced and this controls efficient Maraba virus binding and entry into infected cells. Taken together, these results are the first to implicate the potential impact of differential viral oncolytic properties at key steps of ovarian cancer metastasis.

Original languageEnglish (US)
Article number15013
Number of pages1
JournalMolecular Therapy - Oncolytics
Volume2
DOIs
StatePublished - Sep 23 2015
Externally publishedYes

Fingerprint

Neoplasm Metastasis
Myxoma virus
Ovarian Neoplasms
Viruses
Vaccinia virus
Oncolytic Viruses
Virus Attachment
Vaccinia
Virus Internalization
In Vitro Techniques
Ovarian epithelial cancer
LDL Receptors
Suspensions
Carcinoma
Cell Line
Neoplasms

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Evidence for differential viral oncolytic efficacy in an in vitro model of epithelial ovarian cancer metastasis. / Tong, Jessica G.; Valdes, Yudith Ramos; Barrett, John W.; Bell, John C.; Stojdl, David; McFadden, Douglas; McCart, J. Andrea; DiMattia, Gabriel E.; Shepherd, Trevor G.

In: Molecular Therapy - Oncolytics, Vol. 2, 15013, 23.09.2015.

Research output: Contribution to journalArticle

Tong, Jessica G. ; Valdes, Yudith Ramos ; Barrett, John W. ; Bell, John C. ; Stojdl, David ; McFadden, Douglas ; McCart, J. Andrea ; DiMattia, Gabriel E. ; Shepherd, Trevor G. / Evidence for differential viral oncolytic efficacy in an in vitro model of epithelial ovarian cancer metastasis. In: Molecular Therapy - Oncolytics. 2015 ; Vol. 2.
@article{af6cc35313204337b2061fc46eb8274b,
title = "Evidence for differential viral oncolytic efficacy in an in vitro model of epithelial ovarian cancer metastasis",
abstract = "Epithelial ovarian cancer is unique among most carcinomas in that metastasis occurs by direct dissemination of malignant cells traversing throughout the intraperitoneal fluid. Accordingly, we test new therapeutic strategies using an in vitro three-dimensional spheroid suspension culture model that mimics key steps of this metastatic process. In the present study, we sought to uncover the differential oncolytic efficacy among three different viruses-Myxoma virus, double-deleted vaccinia virus, and Maraba virus-using three ovarian cancer cell lines in our metastasis model system. Herein, we demonstrate that Maraba virus effectively infects, replicates, and kills epithelial ovarian cancer (EOC) cells in proliferating adherent cells and with slightly slower kinetics in tumor spheroids. Myxoma virus and vaccinia viruses infect and kill adherent cells to a much lesser extent than Maraba virus, and their oncolytic potential is almost completely attenuated in spheroids. Myxoma virus and vaccinia are able to infect and spread throughout spheroids, but are blocked in the final stages of the lytic cycle, and oncolytic-mediated cell killing is reactivated upon spheroid reattachment. Alternatively, Maraba virus has a remarkably reduced ability to initially enter spheroid cells, yet rapidly infects and spreads throughout spheroids generating significant cell killing effects. We show that low-density lipoprotein receptor expression in ovarian cancer spheroids is reduced and this controls efficient Maraba virus binding and entry into infected cells. Taken together, these results are the first to implicate the potential impact of differential viral oncolytic properties at key steps of ovarian cancer metastasis.",
author = "Tong, {Jessica G.} and Valdes, {Yudith Ramos} and Barrett, {John W.} and Bell, {John C.} and David Stojdl and Douglas McFadden and McCart, {J. Andrea} and DiMattia, {Gabriel E.} and Shepherd, {Trevor G.}",
year = "2015",
month = "9",
day = "23",
doi = "10.1038/mto.2015.13",
language = "English (US)",
volume = "2",
journal = "Molecular Therapy - Oncolytics",
issn = "2372-7705",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Evidence for differential viral oncolytic efficacy in an in vitro model of epithelial ovarian cancer metastasis

AU - Tong, Jessica G.

AU - Valdes, Yudith Ramos

AU - Barrett, John W.

AU - Bell, John C.

AU - Stojdl, David

AU - McFadden, Douglas

AU - McCart, J. Andrea

AU - DiMattia, Gabriel E.

AU - Shepherd, Trevor G.

PY - 2015/9/23

Y1 - 2015/9/23

N2 - Epithelial ovarian cancer is unique among most carcinomas in that metastasis occurs by direct dissemination of malignant cells traversing throughout the intraperitoneal fluid. Accordingly, we test new therapeutic strategies using an in vitro three-dimensional spheroid suspension culture model that mimics key steps of this metastatic process. In the present study, we sought to uncover the differential oncolytic efficacy among three different viruses-Myxoma virus, double-deleted vaccinia virus, and Maraba virus-using three ovarian cancer cell lines in our metastasis model system. Herein, we demonstrate that Maraba virus effectively infects, replicates, and kills epithelial ovarian cancer (EOC) cells in proliferating adherent cells and with slightly slower kinetics in tumor spheroids. Myxoma virus and vaccinia viruses infect and kill adherent cells to a much lesser extent than Maraba virus, and their oncolytic potential is almost completely attenuated in spheroids. Myxoma virus and vaccinia are able to infect and spread throughout spheroids, but are blocked in the final stages of the lytic cycle, and oncolytic-mediated cell killing is reactivated upon spheroid reattachment. Alternatively, Maraba virus has a remarkably reduced ability to initially enter spheroid cells, yet rapidly infects and spreads throughout spheroids generating significant cell killing effects. We show that low-density lipoprotein receptor expression in ovarian cancer spheroids is reduced and this controls efficient Maraba virus binding and entry into infected cells. Taken together, these results are the first to implicate the potential impact of differential viral oncolytic properties at key steps of ovarian cancer metastasis.

AB - Epithelial ovarian cancer is unique among most carcinomas in that metastasis occurs by direct dissemination of malignant cells traversing throughout the intraperitoneal fluid. Accordingly, we test new therapeutic strategies using an in vitro three-dimensional spheroid suspension culture model that mimics key steps of this metastatic process. In the present study, we sought to uncover the differential oncolytic efficacy among three different viruses-Myxoma virus, double-deleted vaccinia virus, and Maraba virus-using three ovarian cancer cell lines in our metastasis model system. Herein, we demonstrate that Maraba virus effectively infects, replicates, and kills epithelial ovarian cancer (EOC) cells in proliferating adherent cells and with slightly slower kinetics in tumor spheroids. Myxoma virus and vaccinia viruses infect and kill adherent cells to a much lesser extent than Maraba virus, and their oncolytic potential is almost completely attenuated in spheroids. Myxoma virus and vaccinia are able to infect and spread throughout spheroids, but are blocked in the final stages of the lytic cycle, and oncolytic-mediated cell killing is reactivated upon spheroid reattachment. Alternatively, Maraba virus has a remarkably reduced ability to initially enter spheroid cells, yet rapidly infects and spreads throughout spheroids generating significant cell killing effects. We show that low-density lipoprotein receptor expression in ovarian cancer spheroids is reduced and this controls efficient Maraba virus binding and entry into infected cells. Taken together, these results are the first to implicate the potential impact of differential viral oncolytic properties at key steps of ovarian cancer metastasis.

UR - http://www.scopus.com/inward/record.url?scp=85006091110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006091110&partnerID=8YFLogxK

U2 - 10.1038/mto.2015.13

DO - 10.1038/mto.2015.13

M3 - Article

AN - SCOPUS:85006091110

VL - 2

JO - Molecular Therapy - Oncolytics

JF - Molecular Therapy - Oncolytics

SN - 2372-7705

M1 - 15013

ER -