title: Transient receptor potential vanilloid 4 (TRPV4) is downregulated in keratinocytes in human non-melanoma skin cancer.
abstract: A subgroup of the transient receptor potential (TRP) channels, including vanilloid 1 (TRPV1), TRPV2, TRPV3, TRPV4, and TRP ankyrin 1 (TRPA1), is expressed in cutaneous peptidergic somatosensory neurons, and has been found in skin non-neuronal cells, such as keratinocytes. Different cancer cells express TRPs, where they may exert either pro- or antitumorigenic roles. Expression and function of TRPs in skin cancers have been, however, poorly investigated. Here, we have studied the distribution and expression of TRPs by immunohistochemistry and messenger RNA (mRNA) in human healthy skin and human keratinocytic tumors, including intraepidermal proliferative disorders (solar keratosis (SK) and Bowen's disease), and non-melanoma skin cancer (NMSC; basal cell and squamous cell carcinomas). Similar TRPV1, TRPV2, and TRPV3 staining was found in keratinocytes from healthy and tumor tissues. TRPA1 staining was increased solely in SK samples. However, the marked TRPV4 staining and TRPV4 mRNA expression, observed in healthy or inflamed skin, was abrogated both in premalignant lesions and NMSC. In a human keratinocyte cell line (HaCaT), TRPV4 stimulation released IL-8, which in turn downregulated TRPV4 expression. Selective reduction in TRPV4 expression could represent an early biomarker of skin carcinogenesis. Whether the cytokine-dependent, autocrine pathway that results in TRPV4 downregulation contributes to NMSC mechanism remains to be determined.
authors.affiliation: Department of Health Sciences, Clinical Pharmacology and Oncology Unit, University of Florence, Florence, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Fusi
authors.affiliation: Department of Health Sciences, Clinical Pharmacology and Oncology Unit, University of Florence, Florence, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Materazzi
authors.affiliation: Department of Health Sciences, Clinical Pharmacology and Oncology Unit, University of Florence, Florence, Italy.
authors.forename: Daiana
authors.initials: D
authors.lastname: Minocci
authors.affiliation: Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Maio
authors.affiliation: Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Oranges
authors.affiliation: Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy. Electronic address: daniela.massi@unifi.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.affiliation: Department of Health Sciences, Clinical Pharmacology and Oncology Unit, University of Florence, Florence, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Nassini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019898:Autocrine Communication / Q000276:immunology; D002280:Basal Cell Carcinoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D007642:Keratosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050916:TRPV Cation Channels / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014015:Tissue Banks
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human