title: Hair follicle disruption facilitates pathogenesis to UVB-induced cutaneous inflammation and basal cell carcinoma development in Ptch(+/-) mice.
abstract: Hairless mice carrying homozygous mutations in hairless gene manifest rudimentary hair follicles (HFs), epidermal cysts, hairless phenotype, and enhanced susceptibility to squamous cell carcinomas. However, their susceptibility to basal cell carcinomas (BCCs), a neoplasm considered originated from HF-localized stem cells, is unknown. To demonstrate the role of HFs in BCC development, we bred Ptch(+/-)/C57BL6 with SKH-1 hairless mice, followed by brother-sister cross to get F2 homozygous mutant (hairless) or wild-type (haired) mice. UVB-induced inflammation was less pronounced in shaved haired than in hairless mice. In hairless mice, inflammatory infiltrate was found around the rudimentary HFs and epidermal cysts. Expression of epidermal IL1f6, S100a8, vitamin D receptor, repetin, and major histocompatibility complex II, biomarkers depicting susceptibility to cutaneous inflammation, was also higher. In these animals, HF disruption altered susceptibility to UVB-induced BCCs. Tumor onset in hairless mice was 10 weeks earlier than in haired littermates. The incidence of BCCs was significantly higher in hairless than in haired animals; however, the magnitude of sonic hedgehog signaling did not differ significantly. Overall, 100% of hairless mice developed >12 tumors per mouse after 32 weeks of UVB therapy, whereas haired mice developed fewer than three tumors per mouse after 44 weeks of long-term UVB irradiation. Tumors in hairless mice were more aggressive than in haired littermates and manifested decreased E-cadherin and enhanced mesenchymal proteins. These data provide novel evidence that disruption of HFs in Ptch(+/-) mice enhances cutaneous susceptibility to inflammation and BCCs.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Weng
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Aadithya
authors.initials: A
authors.lastname: Arumugam
authors.affiliation: Department of Dermatology, Columbia University, New York, New York.
authors.forename: Xiuwei
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Sandeep C
authors.initials: SC
authors.lastname: Chaudhary
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Changzhao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Dermatology, Columbia University, New York, New York.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Christiano
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Elmets
authors.affiliation: Department of Dermatology, Columbia University, New York, New York.
authors.forename: David R
authors.initials: DR
authors.lastname: Bickers
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address: mathar@uab.edu.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Athar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D002280:Basal Cell Carcinoma / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D018859:Hair Follicle / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D053823:Hedgehog Proteins / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D008297:Male; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000473:pathology*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D012867:Skin / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D012460:Sulfasalazine / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D016328:NF-kappa B; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C465570:Shh protein, mouse; D012460:Sulfasalazine