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Papillomavirus-Colonized Murine Skin Confers Cancer Resistance

ABSTRACT: Herein we hypothesize that there are distinct gene expression changes that occur following MmuPV1 skin colonization that activates antiviral immune mechanisms capable of suppressing tumor growth.

ORGANISM(S): Mus musculus

PROVIDER: GSE128476 | GEO | 2019/10/25

REPOSITORIES: GEO

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Project description:Papillomaviruses (PVs) are able to induce papillomas, premalignant lesions, and carcinomas in a wide variety of species. PVs are classified first based on their host and tissue tropism and then their genomic diversities. A laboratory mouse papillomavirus, MmuPV1 (formerly MusPV), naturally infects NMRI-Foxn1nu/Foxn1nu (nude; T cell deficient) mice. C57BL/6J wild-type mice were not susceptible to MmuPV1 infection; however, immunocompetent, alopecic, S/RV/Cri-ba/ba (bare) mice developed small papillomas at injection sites that regressed. NMRI-Foxn1nu and B6.Cg-Foxn1nu but not NU/J-Foxn1nu mice were susceptible to MmuPV1 infection. B6 congenic strains, but not other congenic strains carrying the same allelic mutations, that lack B- and T-cells, but not B-cells alone, were susceptible to infection, indicating that mouse strain and T-cell deficiency are critical to tumor formation. Although lesions initially observed were exophytic papillomas around the muzzle, exophytic papillomas on the tail and condylomas of the vaginal lining could be induced by experimental infections. On the dorsal skin, locally invasive, poorly differentiated tumors developed with features similar to human trichoblastomas. Transcriptome analysis revealed significant differences between the normal skin in these anatomic sites and in papillomas versus trichoblastomas. The primarily dysregulated genes involved molecular pathways associated with cancer, cellular development, cellular growth and proliferation, cell morphology, and connective tissue development and function. Surprisingly, few of the genes commonly associated with basal cell carcinoma or squamous cells carcinoma were dramatically dysregulated. To determine if there were transcriptome differences between papillomas on the tail skin compared to invasive trichoblastomas on the dorsal skin, tumors from the tail and dorsal skin from 3 B6.Cg-Foxn1nu/Foxn1nu mice and unaffected skin from the tail or contra-lateral (dorsal skin) were compared using the Affymetrix GeneChip Mouse Genome 1.0 ST Array. Concurrently, a matched study was done at the University of Louisville comparing facial (muzzle) papillomas and dorsal skin trichoblastomas to respective unaffected contralateral skin.

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Papillomavirus-Colonized Murine Skin Confers Cancer Resistance

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