Molecular interactions of B-CAM (basal-cell adhesion molecule) and laminin in epithelial skin cancer.
Molecular events underlying the progression of malignant tumors through the surrounding tissue are largely mediated by membrane-bound adhesion molecules. Basal-cell adhesion molecule (B-CAM), a 90-kDa laminin receptor of the immunoglobulin superfamily, is induced in some epithelial malignancies. Its function in these tumors, however, still remains obscure. We demonstrated that expression of B-CAM is very weak, if detectable at all, in normal epidermis but is strongly induced in both basal cell carcinomas and squamous cell carcinomas of the skin, and most pronounced at the basal surface of the tumor nests. Interestingly, the only known B-CAM ligand, laminin, was markedly upregulated within corresponding microanatomical sites surrounding the tumor nests, suggesting that both molecules may interact there. Consistent with this hypothesis, we were able to directly demonstrate binding of a B-CAM/Fc chimeric molecule to the peritumoral stroma in situ. Finally, in proof-of-principle experiments, human B-CAM was overexpressed both in murine and in human fibroblasts. The haptotactic migration of these novel B-CAM+ cell populations on a laminin matrix was significantly increased (P = 0.02) as compared to mock-transfected cells when integrin-mediated adhesion was blocked by chelation of divalent cations. Thus, our findings provide the first direct experimental evidence that interactions of B-CAM and laminin may be involved in progression of epithelial skin tumors.
Drewniok
Claudia
C
Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine and Department of Dermatology, University of Würzburg, Würzburg, Germany.
Wienrich
B Gregor
BG
Schön
Margarete
M
Ulrich
Jens
J
Zen
Qin
Q
Telen
Marilyn J
MJ
Hartig
Roland J
RJ
Wieland
Ilse
I
Gollnick
Harald
H
Schön
Michael P
MP
D000818:Animals; D002280:Basal Cell Carcinoma / Q000209:etiology / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin / Q000378:metabolism*; D008024:Ligands; D008188:Lutheran Blood-Group System; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
C090228:BCAM protein, human; D015815:Cell Adhesion Molecules; D007797:Laminin; D008024:Ligands; D008188:Lutheran Blood-Group System; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins