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

FEBS J. 2013 May;280(10):2342-52. doi: 10.1111/febs.12179. Epub 2013 Mar 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / metabolism
  • Bone Marrow / enzymology
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Cell Adhesion
  • Cell Line, Tumor
  • Chondroitin ABC Lyase / pharmacology
  • Collagen Type I / metabolism*
  • Culture Media / metabolism
  • Flow Cytometry
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Multiple Myeloma / enzymology
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Protein Binding
  • Protein Interaction Mapping
  • Proteoglycans / antagonists & inhibitors
  • Proteoglycans / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Vesicular Transport Proteins / antagonists & inhibitors
  • Vesicular Transport Proteins / metabolism*

Substances

  • Antibodies
  • Collagen Type I
  • Culture Media
  • Proteoglycans
  • RNA, Messenger
  • Vesicular Transport Proteins
  • serglycin
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Chondroitin ABC Lyase