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© The Rockefeller University Press, 0021-9525/1998//267 $5.00
The Journal of Cell Biology, Volume 141, Number 1, , 1998 267-280

Regular Articles

Association Between the Rat Homologue of CO-029, a Metastasis-associated Tetraspanin Molecule and Consumption Coagulopathy



Christoph Claas*, Simone Seiter*,§, Andreas Claas{ddagger}, Larissa Savelyeva{ddagger}, Manfred Schwab{ddagger}, and Margot Zöller*,||

* Department of Tumorprogression and Immune Defense and {ddagger} Department of Cytogenetics, German Cancer Research Center, 69120 Heidelberg, Germany; § Department of Dermatology, University Hospital, 66421 Homburg, Germany; and || Department of Applied Genetics, University of Karlsruhe, 76131 Karlsruhe, Germany

Recently, we have described a panel of metastasis-associated antigens in the rat, i.e., of molecules expressed on metastasizing, but not on nonmetastasizing tumor lines. One of these molecules, recognized by the monoclonal antibody D6.1 and named accordingly D6.1A, was found to be abundantly expressed predominantly on mesenchyme-derived cells. The DNA of the antigen has been isolated and cloned. Surprisingly, the gene product proved to interfere strongly with coagulation.

The 1.182-kb cDNA codes for a 235–amino acid long molecule with a 74.2% homology in the nucleotide and a 70% homology in the amino acid sequence to CO-029, a human tumor-associated molecule. According to the distribution of hydrophobic and hydrophilic amino acids, D6.1A belongs to the tetraspanin superfamily. Western blotting of D6.1A-positive metastasizing tumor lines revealed that the D6.1A, like many tetraspanin molecules, is linked to further membrane molecules, one of which could be identified as {alpha}6β1 integrin. Transfection of a low-metastasizing tumor cell line with D6.1A cDNA resulted in increased metastatic potential and provided a clue as to the functional role of D6.1A. We noted massive bleeding around the metastases and, possibly as a consequence, local infarctions predominantly in the mesenteric region and all signs of a consumption coagulopathy. By application of the D6.1 antibody the coagulopathy was counterregulated, though not prevented.

It has been known for many years that tumor growth and progression is frequently accompanied by thrombotic disorders. Our data suggest that the phenomenon could well be associated with the expression of tetraspanin molecules.

Abbreviations used in this paper: AA, amino acid; AS, BSp73AS tumor line; AS-14, AS-14 tumor line; AS-D6.1A, AS-D6.1A tumor line; ASML, ASML tumor line; CO-I/III/IV, collagen type I/III/IV; FISH, fluorescence in situ hybridization; FN, fibronectin; HA, hyaluronic acid; i.f.p., intrafootpad; LA, laminin; PAC, P1-derived artificial chromosome; PTT, partial prothrombin time; s.c., subcutaneously; PVDF, polyvinylidene difluoride; VN, vitronectin.

This investigation was supported by the Mildred Scheelstiftung für Krebshilfe (M. Zöller) and the Tumorzentrum Heidelberg Mannheim (M. Zöller).


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