Differential expression of laminin isoforms and beta 4 integrin epitopes in the basement membrane zone of normal human skin and basal cell carcinomas.
The basement membrane zone biology of normal human skin and basal cell carcinomas was explored by indirect immunofluorescence with monoclonal antibodies recognizing five subunit polypeptides of three different laminin isoforms as well as the beta 4 integrin epitopes. The laminin antibodies were specific for A, B1, and B2 chains of classic laminin, for the M chain of merosin, or for the S chain in S-laminin. Immunostaining of normal human skin revealed a strong signal with antibodies for A, B1, and B2 chain epitopes. A weak immunosignal was detected with an anti-M chain antibody, whereas the S-chain epitopes were undetectable, even following pretreatment of sections with hyaluronidase. Thus, the laminin at the epidermal-dermal junction of normal human skin is primarily of the classic type, with some merosin molecules being present. The staining of six nodular basal cell carcinomas revealed the presence of A, B1, and B2 chain epitopes in a linear pattern, but, in contrast to normal skin, the antibody recognizing M-chain epitopes yielded a strong immunosignal, and S-chain epitopes could also be readily detected. Staining for beta 4 integrins, potential receptors for laminin, revealed a strong staining reaction in normal skin as well as in the superficial portions of the basal cell carcinoma. However, the immunofluorescence pattern in the deeper portions of the lesions was scattered and interrupted. Thus, altered composition of the basement membrane of nodular basal cell carcinomas with respect to laminin isoforms and their interactions with putative cell-surface receptors, the beta 4 integrins, may change the containment of the tumor islands, contributing to the local aggressive behavior of basal cell carcinomas.
Sollberg
S
S
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Peltonen
J
J
Uitto
J
J
D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism*; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D000939:Epitopes / Q000096:biosynthesis; D006801:Humans; D007124:Immunoenzyme Techniques; D016023:Integrins / Q000096:biosynthesis* / Q000276:immunology; D007797:Laminin / Q000096:biosynthesis*; D012867:Skin / Q000378:metabolism* / Q000648:ultrastructure; D012878:Skin Neoplasms / Q000378:metabolism*
D000939:Epitopes; D016023:Integrins; D007797:Laminin