Basal cell carcinomas display extensive abnormalities in the hemidesmosome anchoring fibril complex.
We have employed a panel of antibodies directed against several newly-defined and well-characterized components of the epidermal basement membrane (BM) to investigate the biology of basal cell carcinoma (BCC) by indirect immunofluorescence and to determine whether alterations in BM components may play a significant role in BCC tumor invasion. We found that the 230 KD bullous pemphigoid antigen (BPA) was either not detected (13/16) or significantly diminished (3/16) in BCC tumor BM. While the 180 KD BPA revealed less intense staining of the normal overlying epidermal BM than did the 230 KD BPA, the 180 KD BPA was uniformly undetectable in BCC tumor BM (16/16). Epiligrin was either not detected (9/15) or minimally detected (6/15) in BCC tumor BM. alpha 6 integrin was not detected (15/16) or minimally detected (1/16) in BCC tumor BM, whereas beta 4 integrin was uniformly undetectable in BCC tumor BM (16/16). Type VII collagen was also not detected (9/16) or was significantly diminished (4/16) in BCC tumor BM. Laminin and type IV collagen were both at least as strong in BCC tumor BM as in adjacent normal BM. All of these components were present both in the epidermis of normal skin as well as in the normal epidermal BM overlying BCC tumor nests. Our findings reveal extensive alterations in numerous components of the hemidesmosome anchoring fibril complex of BCC's. As this complex is thought to play an important part in epidermal cell adhesion to the BM, our findings suggest that these extensive BM abnormalities may facilitate or contribute to BCC tumor invasion.
Korman
N J
NJ
Department of Dermatology, Case Western Reserve University, Cleveland, Ohio 44106.
Hrabovsky
S L
SL
D008841:Actin Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure*; D000951:Antigens, Neoplasm / Q000032:analysis; D001324:Autoantigens / Q000032:analysis; D001485:Basement Membrane / Q000737:chemistry / Q000648:ultrastructure; D014408:Biomarkers, Tumor / Q000032:analysis; D002280:Basal Cell Carcinoma / Q000737:chemistry / Q000648:ultrastructure*; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules / Q000032:analysis; D003094:Collagen; D003598:Cytoskeletal Proteins; D003896:Desmosomes / Q000737:chemistry / Q000648:ultrastructure*; D000071821:Dystonin; D004817:Epidermis / Q000737:chemistry; D016326:Extracellular Matrix Proteins / Q000032:analysis; D006801:Humans; D016023:Integrins / Q000032:analysis; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D012878:Skin Neoplasms / Q000737:chemistry / Q000648:ultrastructure*; D000097794:Kalinin; D000097805:Collagen Type XVII
D000951:Antigens, Neoplasm; D001324:Autoantigens; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D016326:Extracellular Matrix Proteins; D016023:Integrins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097794:Kalinin; D000097805:Collagen Type XVII; C486268:DST protein, human