Expression of members of the novel membrane linked metalloproteinase family ADAM in cells derived from a range of haematological malignancies

Abstract

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 homologues are the type III reprolysin enzymes which have been demonstrated to be, among other things potent type IV collagenases. ADAMs are putative membrane linked proteins with several domains including a metalloproteinase domain, a potential integrin binding domain, a cysteine rich sequence and an EGF like sequence. They have been implicated in a wide variety of functions including basement membrane degradation and cell-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 (K562), lymphoma (U937 and Cupillo) and myeloma (U266B1). We find clear expression of four members of this novel family of proteins but note differences in the expression levels of each member. The ADAMs known as MADM (ADAM10), MCMP (ADAM12, MDC9) and Metargidin (ADAM15) which all possess potentially active metalloproteinase domains are expressed in all these cell types to significant levels. The putative tumour suppressor gene MDC (ADAM11) is expressed at very low levels in all cells examined. As ADAMs may have both potential metalloproteinase activity and adhesive domains we wish to explore the role of these proteins with regard to pathophysiology of haematological malignancy such as egression of leukaemic cells from the bone marrow.