Defective laminin 5 processing in cylindroma cells.
Cylindromas are benign skin tumors occurring as multiple nodules characteristically well circumscribed by an excess of basement membrane-like material. To determine the molecular defects leading to extracellular matrix accumulation, the ultrastructural, immunological, and biochemical properties of cylindroma tissue and isolated cells were analyzed. In cylindromas, hemidesmosomes are reduced in number, heterogeneous and immature compared to the normal dermal-epidermal junction. Expression of the alpha6beta4 integrin in tumor cells is weaker than in basal keratinocytes of the epidermis. Moreover, although in the epidermis alpha2beta1-integrin expression is restricted to the basal cell layer, it is found in all neoplastic cells within the nodules. Laminin 5 is present throughout the whole thickness of the basement membrane-like zone whereas laminin 10 is restricted to the interface adjacent to the tumor cells. Furthermore, laminin 5 is not properly processed and most of the alpha3A and gamma2 laminin chains remain as 165-kd and 155-kd polypeptides, respectively. Mature laminin 5 is thought to be necessary for correct hemidesmosome and basement membrane formation and its abnormal processing, as well as the low expression of alpha6beta4 integrins, could explain the lack of mature hemidesmosomes. Together, the results show that multiple molecular defects, including alteration of laminin 5 and its integrin receptors, contribute to structural aberrations of the basement membrane and associated structures in cylindromas.
Tunggal
Lucy
L
Department of Dermatology, Medical Faculty, Institute for Biochemistry II, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Köln, Germany.
Ravaux
Juliette
J
Pesch
Monika
M
Smola
Hans
H
Krieg
Thomas
T
Gaill
Françoise
F
Sasaki
Takako
T
Timpl
Rupert
R
Mauch
Cornelia
C
Aumailley
Monique
M
D000906:Antibodies; D001485:Basement Membrane / Q000737:chemistry / Q000648:ultrastructure; D003528:Carcinoma, Adenoid Cystic / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism*; D022002:Hemidesmosomes / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000032:analysis / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014407:Tumor Cells, Cultured; D000097794:Kalinin
D000906:Antibodies; D015815:Cell Adhesion Molecules; D016023:Integrins; D007797:Laminin; D000097794:Kalinin; C119013:laminin 10