EXPRESSION OF MEMBERS OF THE NOVEL MEMBRANE LINKED METALLOPROTEINASE FAMILY ADAM IN CELLS DERIVED FROM A RANGE OF HEMATOLOGICAL MALIGNANCIES

ADAMs (A disintegrin and metalloproteinase) are a recently discovered family of proteins with significant primary sequence similarity to the reprolysin family of snake venomases. These ADAMs closest known homol ogues are the type III reprolysin enzymes which have been demonstrated to be, among other things potent type IV collagenases, ADAMs are puta tive membrane linked proteins with several domains including a metallo proteinase domain, a potential integrin binding domain, a cysteine ric h sequence and an EGF like sequence. They have been implicated in a wi de variety of functions including basement membrane degradation and ce ll-cell and cell-matrix interactions. We have used RT-PCR and Northern blotting to characterise the expression of members of this family in cells derived from a variety of haematological malignancies including leukaemia (HL60 and Jurkat), erythroleukaemia (R562), lymphoma (U937 a nd Cupillo) and myeloma (U266B1). We find clear expression of four mem bers of this novel family of proteins but note differences in the expr ession levels of each member. The ADAMs known as MADM (ADAM10), MCMP ( ADAM12, MDC9) and Metargidin (ADAM15) which all possess potentially ac tive metalloproteinase domains are expressed in all these cell types t o significant levels. The putative tumour suppresser gene MDC (ADAM11) is expressed at very low levels in all cells examined. As ADAMs may h ave both potential metalloproteinase activity and adhesive domains we wish to explore the role of these proteins with regard to pathophysiol ogy of haematological malignancy such as egression of leukaemic cells from the bone marrow. (C) 1997 Academic Press.