Mus musculus papillomavirus 1 is a key driver of skin cancer development upon immunosuppression

Autor: Katharina Strasser, Sonja Dorfer, Alessandra Handisurya, Harald Kittler, Michael Bonelli, Wolfgang Bauer, Georg Schröckenfuchs, Christophe Cataisson, Beate M. Lichtenberger, Michael B. Fischer
Rok vydání: 2020
Předmět:
medicine.medical_specialty
Skin Neoplasms
medicine.medical_treatment
infectious disease
Cell
Mice
Nude
030230 surgery
Organ transplantation
Virus
immunosuppressant ‐ calcineurin inhibitor: cyclosporine A (CsA)
Pathogenesis
03 medical and health sciences
Mice
basic (laboratory) research / science
0302 clinical medicine
Basic Science
immunosuppression / immune modulation
infection and infectious agents ‐ viral
medicine
Immunology and Allergy
Animals
Pharmacology (medical)
Dna viral
Papillomaviridae
Immunosuppression Therapy
animal models: murine
Transplantation
business.industry
Papillomavirus Infections
Immunosuppression
medicine.disease
dermatology
medicine.anatomical_structure
cancer / malignancy / neoplasia: skin ‐ nonmelanoma
Infectious disease (medical specialty)
Cancer research
Original Article
Skin cancer
ORIGINAL ARTICLES
business
Zdroj: American Journal of Transplantation
ISSN: 1600-6143
Popis: Epidemiological and experimental data implicate cutaneous human papillomavirus infection as co‐factor in the development of cutaneous squamous cell carcinomas (cSCCs), particularly in immunocompromised organ transplant recipients (OTRs). Herein, we established and characterized a skin cancer model, in which Mus musculus papillomavirus 1 (MmuPV1) infection caused cSCCs in cyclosporine A (CsA)‐treated mice, even in the absence of UV light. Development of cSCCs and their precursors were observed in 70% of MmuPV1‐infected, CsA‐treated mice on back as well as on tail skin. Immunosuppression by systemic CsA, but not UV‐B irradiation, was a prerequisite, as immunocompetent or UV‐B–irradiated mice did not develop skin malignancies after infection. In the virus‐driven cSCCs the MmuPV1‐E6/E7 oncogenes were abundantly expressed, and transcriptional activity and productive infection demonstrated. MmuPV1 infection induced the expression of phosphorylated H2AX, but not degradation of proapoptotic BAK in the cSCCs. Transfer of primary cells, established from a MmuPV1‐induced cSCC from back skin, into athymic nude mice gave rise to secondary cSCCs, which lacked viral DNA, demonstrating that maintenance of the malignant phenotype was virus independent. This papillomavirus‐induced skin cancer model opens future investigations into viral involvement, pathogenesis, and cancer surveillance, aiming at understanding and controlling the high incidence of skin cancer in OTRs.
This murine model demonstrates the synergy of Mus musculus papillomavirus 1 skin infection and systemic immunosuppression in the development of cutaneous squamous cell carcinomas, even in the absence of UV‐B light.
Databáze: OpenAIRE
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