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J. Cell Biol.,
Volume 141, Number 1, April 6, 1998 267-280
* Department of Tumorprogression and Immune Defense and 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 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.
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
6
1 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.
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