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Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314

Oncogene volume 18, pages 2323–2334 (1999)Cite this article

Abstract

Screening for surface molecules expressed by metastasizing rat tumors had revealed evidence for metastasis-association of a molecule also expressed on epithelial cells. The similarity to the expression profile of the panepithelial glycoprotein EGP314 prompted us to isolate and sequence the gene and to explore functional features of the molecule in transfected tumor lines. The molecule D5.7A, named according to the antibody, D5.7, used for selection, indeed, is the ortholog of EGP314 with 92% and 80% identity to the murine and the human molecules. Like EGP314, D5.7A has a particular cleavage site, a small cleavage product being resolved under reducing conditions from the membrane anchored part of the molecule. Transfection of a low metastasizing fibrosarcoma, pheochromoblastoma and adenocarcinoma revealed that expression of D5.7A facilitates tumor progression. Depending on the origin of the tumor, D5.7A transfectants either metastasized via the lymphatic system (pheochromoblastoma, adenocarcinoma) or hematogeneously (fibrosarcoma). Particularly after proteolytic cleavage, D5.7A facilitated cell – cell adhesion and provided a proliferative signal upon crosslinking. Thus, the rat ortholog of EGP314 is involved in metastasis formation. Importantly, its functional activities apparently rely on proteolytic cleavage. These findings provide a first evidence on how a panepithelial marker can be involved in tumor progression.

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Abbreviations

BSA:

bovine serum albumin

FCS:

fetal calf serum

i.f.p.:

intrafootpad

mAB:

monoclonal antibody

PROG:

progressor

RG:

regressor

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Acknowledgements

This investigation was supported by the Mildred Scheelstiftung für Krebshilfe (MZ) and the Tumorzentrum Heidelberg Mannheim (MZ). We thank Dr S Matzku, Merck AG, Darmstadt, for helpful suggestions and discussion during preparation of the manuscript and K Hexel, Department of Immune Genetics, German Cancer Research Center, Heidelberg, for fluorescence activated cell sorting. The nucleotide sequence reported in this manuscript has been submitted to EMBL with the accession number AJ001044.

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Authors and Affiliations

  1. Department of Tumor Progression and Immune Defense, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    J Würfel, M Rösel, C Claas, M Herlevsen, R Weth & M Zöller

  2. Department of Dermatology, University Hospital, Homburg, Germany

    S Seiter

  3. Department of Applied Genetics, University of Karlsruhe, Germany

    M Zöller

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  1. J Würfel
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Würfel, J., Rösel, M., Seiter, S. et al. Metastasis-association of the rat ortholog of the human epithelial glycoprotein antigen EGP314. Oncogene 18, 2323–2334 (1999). https://doi.org/10.1038/sj.onc.1202542

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