Serglycin (SG) is mainly expressed by hematopoetic cells as an intracellular proteoglycan. Multiple myeloma cells constitutively secrete SG, which in some cell lines is also localized on cell surface. In this study, isolated SG from myeloma cells was found to interact with collagen type I (Col I), which is a major bone matrix component. Notably, cell surface SG (csSG) positive myeloma cells significantly adhered to Col I as compared to cells lacking csSG. Removal of csSG following treatment of the cells with chondroitinase ABC or blocking of csSG by a SG-specific polyclonal antibody significantly reduced the adhesion of myeloma cells to Col I. Culturing csSG-positive myeloma cells on Col I coated dishes or in the presence of soluble Col I, a significant up-regulation of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) expression both at mRNA and protein levels was noticed. Importantly, MMP-9 and MMP-2 were also expressed in increased amounts by myeloma cells in the bone marrow of multiple myeloma patients. Our data show that csSG of myeloma cells affects key functional properties, such as adhesion to Col I, and the expression of MMPs and imply that csSG may serve as a potential prognostic factor and / or target for pharmacological interventions in multiple myeloma. © 2013 The Authors Journal compilation © 2013 FEBS.