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Molecular interactions of B-CAM (basal-cell adhesion molecule) and laminin in epithelial skin cancer

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Abstract

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.

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Fig. 1a–d
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Abbreviations

BCC:

Basal cell carcinoma

SCC:

Squamous cell carcinoma

mAb:

Monoclonal antibody

FACS:

Fluorescence activated cell sorter

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Acknowledgements

We thank J. Herz, B. Glas and K. Rohrbach for excellent technical assistance. This work was supported by a Rudolf-Virchow-Award from the Deutsche Forschungsgemeinschaft and a grant from the Deutsche Krebshilfe to MPS (10-1765-Schö 1) and a Research grant from Sachsen-Anhalt to M.S. C.D., M.S., R.J.H., H.G. and M.P.S. are members of the Forschungszentrum Immunologie Sachsen-Anhalt (grant BMBF 01ZZ0110).

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Authors and Affiliations

  1. Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine and Department of Dermatology, University of Würzburg, 97078, Würzburg, Germany

    Claudia Drewniok, B. Gregor Wienrich, Margarete Schön & Michael P. Schön

  2. Department of Dermatology and Venereology, University of Magdeburg, Germany

    Claudia Drewniok, B. Gregor Wienrich, Margarete Schön, Jens Ulrich, Harald Gollnick & Michael P. Schön

  3. Duke Comprehensive Sickle Cell Center, Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Qin Zen & Marilyn J. Telen

  4. Department of Immunology, University of Magdeburg, Germany

    Roland J. Hartig

  5. Department of Human Genetics, University of Magdeburg, Germany

    Ilse Wieland

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  1. Claudia Drewniok
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  2. B. Gregor Wienrich
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  3. Margarete Schön
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  4. Jens Ulrich
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  10. Michael P. Schön
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Correspondence to Michael P. Schön.

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Drewniok, C., Wienrich, B.G., Schön, M. et al. Molecular interactions of B-CAM (basal-cell adhesion molecule) and laminin in epithelial skin cancer. Arch Dermatol Res 296, 59–66 (2004). https://doi.org/10.1007/s00403-004-0481-4

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  • DOI: https://doi.org/10.1007/s00403-004-0481-4

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