Abstract
Fibrosarcoma is a deadly disease in cats and is significantly more often located at classical vaccine injections sites. More rare forms of spontaneous non-vaccination site (NSV) fibrosarcomas have been described and have been found associated to genetic alterations. Purpose of this study was to compare the efficacy of adenoviral gene transfer in NVS fibrosarcoma. We isolated and characterized a NVS fibrosarcoma cell line (Cocca-6A) from a spontaneous fibrosarcoma that occurred in a domestic calico cat. The feline cells were karyotyped and their chromosome number was counted using a Giemsa staining. Adenoviral gene transfer was verified by western blot analysis. Flow cytometry assay and Annexin-V were used to study cell-cycle changes and cell death of transduced cells. Cocca-6A fibrosarcoma cells were morphologically and cytogenetically characterized. Giemsa block staining of metaphase spreads of the Cocca-6A cells showed deletion of one of the E1 chromosomes, where feline p53 maps. Semi-quantitative PCR demonstrated reduction of p53 genomic DNA in the Cocca-6A cells. Adenoviral gene transfer determined a remarkable effect on the viability and growth of the Cocca-6A cells following single transduction with adenoviruses carrying Mda-7/IL-24 or IFN-γ or various combination of RB/p105, Ras-DN, IFN-γ, and Mda-7 gene transfer. Therapy for feline fibrosarcomas is often insufficient for long lasting tumor eradication. More gene transfer studies should be conducted in order to understand if these viral vectors could be applicable regardless the origin (spontaneous vs. vaccine induced) of feline fibrosarcomas.
Highlights
Fibrosarcoma represents 6–12% of all feline tumors [1]
The pathology report described the presence of an irregular dermal-subdermal mass of sheets and streams of spindle cells and small amounts of collagenous stroma, which is compatible with a diagnosis of fibrosarcoma (Fig. 1 A)
Effects of Adenoviral Gene Transfer on Cat Fibrosarcoma We have studied the effects of the transduction of various proteins involved in the cell cycle and apoptosis pathways such as Rb/p105, p130, p53, p18, p19, p21waf-1, p27kip-1, pTEN, and the dominant negative H-RAS Mutant (116Y) (RasDN), as well as of two immunostimulatory cytokines (Mda-7/IL-24, and IFN-c) that were transferred and expressed into the feline cells using adenoviruses
Summary
Fibrosarcoma represents 6–12% of all feline tumors [1]. It is a malignant tumor of mesenchymal origin, derived from fibrous connective tissue with the presence of undifferentiated proliferating fibroblasts in a collagen matrix, which normally develops in soft tissues. Fibrosarcoma tumors are significantly more often located at classical vaccine injections sites on cats. An epidemiologic analysis showed correlation between fibrosarcoma and injection sites for leukosis vaccines [2]. The vaccines generally associated with this disease to date have been the adjuvanted rabies and feline leukemia virus vaccines; association with non-adjuvanted vaccines has been occasionally reported [2]. More rare forms of spontaneous fibrosarcoma have been described and have been found associated to genetic alterations, such as allelic loss, point mutations and translocations [3,4]
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