title: Expression of the Ly6/uPAR-domain proteins C4.4A and Haldisin in non-invasive and invasive skin lesions.
abstract: C4.4A and Haldisin belong to the Ly6/uPAR/α-neurotoxin protein domain family. They exhibit highly regulated expression profiles in normal epidermis, where they are confined to early (C4.4A) and late (Haldisin) squamous differentiation. We have now explored if dysregulated expressions occur in non-invasive and invasive skin lesions. In non-invasive lesions, their expression signatures were largely maintained as defined by that of normal epidermis. The scenario was, however, markedly different in the progression towards invasive squamous cell carcinomas. In its non-invasive stage (carcinoma in situ), a pronounced attenuation of C4.4A expression was observed, but upon transition to malignant invasive squamous cell carcinomas, the invasive fronts regained high expression of C4.4A. A similar progression was observed for the early stages of benign infiltrating keratoacanthomas. Interestingly, this transition was accompanied by a shift in the predominant association of C4.4A expression with CK1/10 in the normal epidermis to CK5/14 in the invasive lesions. In contrast, Haldisin expression maintained its confinement to the most-differentiated cells and was hardly expressed in the invasive lesions. Because this altered expression of C4.4A was seen in the invasive front of benign (keratoacanthomas) and malignant (squamous cell carcinomas) neoplasms, we propose that this transition of expression is primarily related to the invasive process.
authors.affiliation: The Finsen Laboratory, Rigshospitalet & Biotech Research and Innovation Centre, Copenhagen Biocenter, Copenhagen, Denmark (MCK, MP)
authors.forename: Mette C
authors.initials: MC
authors.lastname: Kriegbaum
authors.affiliation: TDepartment of Pathology, Oslo University Hospital, University of Oslo, Oslo, Norway (OPFC)
authors.forename: Ole P F
authors.initials: OP
authors.lastname: Clausen
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway (ODL)
authors.forename: Ole D
authors.initials: OD
authors.lastname: Lærum
authors.affiliation: The Finsen Laboratory, Rigshospitalet & Biotech Research and Innovation Centre, Copenhagen Biocenter, Copenhagen, Denmark (MCK, MP)|Danish-Chinese Centre for Proteases and Cancer (MP)
authors.forename: Michael
authors.initials: M
authors.lastname: Ploug
mesh_terms: D002280:Basal Cell Carcinoma / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D058851:GPI-Linked Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007636:Keratoacanthoma / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009506:Nevus / Q000378:metabolism / Q000473:pathology; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; C472589:LYPD3 protein, human; C585232:LYPD5 protein, human; D055293:Receptors, Urokinase Plasminogen Activator
keywords: C4.4A; Haldisin; LYPD3; LYPD5; PRO4356; cytokeratins; invasive front; skin lesions; stratum granulosum; stratum spinosum