ASSOCIATION BETWEEN THE RAT HOMOLOG OF CO-029, A METASTASIS-ASSOCIATED TETRASPANIN MOLECULE AND CONSUMPTION COAGULOPATHY

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 th e monoclonal antibody D6.1 and named accordingly D6.1A, was found to b e abundantly expressed predominantly on mesenchyme-derived cells. The DNA of the antigen has been isolated and cloned. Surprisingly, the gen e 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-02 9, a human tumor-associated molecule. According to the distribution of hydrophobic and hydrophilic amino acids, D6.1A belongs to the tetrasp anin superfamily. Western blotting of D6.1A-positive metastasizing tum or lines revealed that the D6.1A, like many tetraspanin molecules, is linked to further membrane molecules, one of which could be identified as alpha 6 beta 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 massi ve bleeding around the metastases and, possibly as a consequence, loca l infarctions predominantly in the mesenteric region and all signs of a consumption coagulopathy. By application of the D6.1 antibody the co agulopathy was counterregulated, though not prevented. It has been kno wn for many years that tumor growth and progression is frequently acco mpanied by thrombotic disorders. Our data suggest that the phenomenon could well be associated with the expression of tetraspanin molecules.