Expression pattern of the bullous pemphigoid-180 antigen in normal and neoplastic epithelia

Abstract

BP180 is a 180kDa hemidesmosomal protein recognized by bullous pemphigoid (BP) and pemphigoid gestationis (PG) autoantibodies. Recent cloning and sequence analysis performed by our laboratory have revealed that BP180 is a transmembrane protein with a long extracellular collagen-like region. A rabbit polyclonal antibody has been generated against a recombinant protein, designated GST-N delta 1, containing a segment of the BP180 ectodomain. The resulting antiserum, RN delta 1A, was shown to specifically react with BP180 on immunoblot, and labelled the extracellular region of the epidermal hemidesmosome on immunoelectron microscopy. A panel of normal and neoplastic human tissues were analysed by indirect immunofluorescence (IF) and RN delta 1A, to determine the distribution of BP180. A total of nine basal cell carcinomas (BCCs) and four squamous cell carcinomas (SCCs) of the skin were also studied. Intense IF staining was seen along the basement membrane zone (BMZ) of the epidermis, hair follicles, and the periphery of sebaceous gland lobules. The sebaceous lobules showed more intense staining in areas close to the duct. The epithelial BMZ of the following tissues also reacted with RN delta 1A: cornea, ocular conjunctiva, buccal mucosa, upper oesophagus, placenta (amnion placentum), umbilical cord and transitional epithelium of the bladder. The epithelium of the jejunum and ovary failed to react with RN delta 1A. Staining of the BCCs and SCCs was variable. Five of six nodular BCCs showed some anti-BP180 staining at the tumour-stromal interface, although the level of staining was less intense than that observed in the overlying normal epidermis. All three morphoeic BCCs analysed in this investigation did not show any staining with RN delta 1A. Three of four SCCs showed weak staining at the tumour-stromal interface. Thus, the tissue distribution of BP180 paralleled that of hemidesmosomes, and expression of this protein was found to be decreased or absent in cutaneous neoplasms.

180-kD bullous pemphigoid antigen/type XVII collagen: Tissue-specific expression and molecular interactions with keratin 18

“…Nevertheless, in the yeast two-hybrid system, the interactions must occur between discrete individual polypeptides, since the interacting clones in the activation domain were retransformed, and the interactions were confirmed using purified plasmids. Previous studies have clearly demonstrated that BPAG2 is the major component of hemidesmosomes at the dermal-epidermal basement membrane zone, while immunohistochemical analyses have suggested more widespread distribution [Nishizawa et al, 1993;Fairley et al, 1995]. Utilizing multiple-tissue mRNA blots and multi-tissue cDNA panels, we demonstrated that BPAG2 is expressed in a variety of tissues with prominent epithelial component.…”

“…In addition, the epithelial basement membranes of cornea [Gordon et al, 1997], ocular conjunctiva, buccal mucosa, upper esophagus, placenta, umbilical cord, and transitional epithelium of the bladder have been shown to express BPAG2, when examined by immunofluorescence staining with antibodies recognizing BPAG2 epitopes [Fairley et al, 1995]. However, the expression of the corresponding gene at the mRNA level has not been examined in detail.…”

Ectodomain Shedding Generates Neoepitopes on Collagen XVII, the Major Autoantigen for Bullous Pemphigoid

“…Transmembrane collagen XVII, also known as BP180 or BPAG2, is widely expressed in skin (6)(7)(8), cornea (7,9), teeth (10), buccal and esophageal mucous membranes (7), brain (11), placenta, and umbilical cord (7). Among these tissues, collagen XVII plays the most important role in the skin, where it is a component of hemidesmosomes in basal keratinocytes and provides stable adhesion between the epidermis and the dermis.…”

Malignancy in Relation to Autoimmune Blistering Dermatoses: Molecular and Clinical Aspects

“…As it was demonstrated that expression of BP180 was decreased or absent in cutaneous neoplasms [184], some authors speculated that some type of carcinomas itself might expose BP180 antigenic epitope, which would normally be hidden, thus inducing the production of autoantibodies that lead to the onset of BP [185]. It was proposed that BP180 neoexpression could be associated with early/malignant transformation of keratinocytes as widely expression of BP180 was demonstrated in SCC in contrast to normal skin, where this protein is restricted to basal keratinocytes [186].…”