title: Persistent Morbillivirus Infection Leads to Altered Cortactin Distribution in Histiocytic Sarcoma Cells with Decreased Cellular Migration Capacity.
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.
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Vanessa Maria
authors.initials: VM
authors.lastname: Pfankuche
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Sayed-Ahmed
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Vanessa Bono
authors.initials: VB
authors.lastname: Contioso
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Spitzbarth
authors.affiliation: Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Rohn
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Ulrich
authors.affiliation: Department of Non-Clinical Drug Safety, Boehringer Ingelheim Pharma GmbH&Co KG, Biberach (Riß), Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Deschl
authors.affiliation: Department of Non-Clinical Drug Safety, Boehringer Ingelheim Pharma GmbH&Co KG, Biberach (Riß), Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Kalkuhl
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.|Center for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Puff
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D051356:Cortactin / Q000096:biosynthesis*; D004216:Distemper / Q000378:metabolism* / Q000473:pathology; D004217:Distemper Virus, Canine / Q000378:metabolism*; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D054747:Histiocytic Sarcoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis*
chemical_list: D051356:Cortactin; D009363:Neoplasm Proteins