Cell-surface serglycin promotes adhesion of myeloma cells to collagen type i and affects the expression of matrix metalloproteinases

Abstract

Serglycin (SG) is mainly expressed by hematopoetic cells as an intracellular proteoglycan. Multiple myeloma cells constitutively secrete SG, which is also localized on the cell surface in some cell lines. In this study, SG isolated from myeloma cells was found to interact with collagen type I (Col I), which is a major bone matrix component. Notably, myeloma cells positive for cell-surface SG (csSG) adhered significantly to Col I, compared to cells lacking csSG. Removal of csSG by treatment of the cells with chondroitinase ABC or blocking of csSG by an SG-specific polyclonal antibody significantly reduced the adhesion of myeloma cells to Col I. Significant up-regulation of expression of the matrix metalloproteinases MMP-2 and MMP-9 at both the mRNA and protein levels was observed when culturing csSG-positive myeloma cells on Col I-coated dishes or in the presence of soluble Col I. MMP-9 and MMP-2 were also expressed in increased amounts by myeloma cells in the bone marrow of patients with multiple myeloma. Our data indicate 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. Serglycin is a major proteoglycan synthesized by myeloma cells that interacts with collagen type I (Col I). Serglycin is localized on the cell surface in some myeloma cells and promotes their adhesion to Col I. The interaction of myeloma cells with Col I through cell-surface associated serglycin affects the expression of MMP-9 and MMP-2, which are highly expressed by myeloma cells in vivo. © 2013 The Authors Journal compilation © 2013 FEBS.