Abstract
Histiocytic sarcomas represent rare but fatal neoplasms in humans. Based on the absence of a commercially available human histiocytic sarcoma cell line the frequently affected dog displays a suitable translational model. Canine distemper virus, closely related to measles virus, is a highly promising candidate for oncolytic virotherapy. Therapeutic failures in patients are mostly associated with tumour invasion and metastasis often induced by misdirected cytoskeletal protein activities. Thus, the impact of persistent canine distemper virus infection on the cytoskeletal protein cortactin, which is frequently overexpressed in human cancers with poor prognosis, was investigated in vitro in a canine histiocytic sarcoma cell line (DH82). Though phagocytic activity, proliferation and apoptotic rate were unaltered, a significantly reduced migration activity compared to controls (6 hours and 1 day after seeding) accompanied by a decreased number of cortactin mRNA transcripts (1 day) was detected. Furthermore, persistently canine distemper virus infected DH82 cells showed a predominant diffuse intracytoplasmic cortactin distribution at 6 hours and 1 day compared to controls with a prominent membranous expression pattern (p ≤ 0.05). Summarized, persistent canine distemper virus infection induces reduced tumour cell migration associated with an altered intracellular cortactin distribution, indicating cytoskeletal changes as one of the major pathways of virus-associated inhibition of tumour spread.
Highlights
Neoplastic disorders still represent one of the most common causes of death in humans as well as in companion animals such as dogs and cats [1,2]
The aim of the present study was to determine the impact of canine distemper virus (CDV) infection on cell migration of canine histiocytic sarcoma cells (DH82 cells) with special emphasis on cortactin expression, gene regulation and possible functional implications
CDV infected DH82 cells exhibited a median percentage of infected cells of 94.15% at 1d post seeding, 96.02% at 3d post seeding and 94.58% at 5d post seeding, whereas no CDV-immunoreactivity was detected in non-infected controls at any time point (Fig 1A and 1B)
Summary
Neoplastic disorders still represent one of the most common causes of death in humans as well as in companion animals such as dogs and cats [1,2]. Despite a wide range of therapeutic approaches including surgery, chemo- and radiotherapy, many tumour types still. Reduced Migration in Morbillivirus-Infected Histiocytic Sarcoma Cells dfg.de/). WBA: This study was in part supported by the Gesellschaft zur Forderung Kynologischer Forschung e.V The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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