The role of proтeoglycans in pathogenesis of multiple myeloma
M.F. Kharchenko, S.S. Bessmeltsev
Russian Research Institute of Hematology and Transfusiology, St. Petersburg
Brief summary
The article comprises the data of literature concerning the roles of transmembrane heparan sulfate proteoglycan syndecan-1 and other proteoglycans in MM. High expression of syndecan-1 (CD138) on the cell surface is one of hallmarks of normal and myeloma plasma cells. Due to the ability to bind and modulate the activity of many effector molecules such as ECM proteins, heparan sulfate-dependent hemopoietic growth factors and cytokines syndecan-1 promotes neoplastic cell growth, survival and dissemination. Syndecan-1 contributes to the adhesion of myeloma cells to bone marrow stroma and takes part in their interactions with hemopoietic microenvironment. This proteoglycan acts on the cell surface and being shed by proteinases it becomes the component of bone marrow plasma, ECM and peripheral blood. The high level of soluble syndecan-1 in serum is considered as independent indicator of poor prognosis of the disease. Due to binding and enhancing the activity of hematopoietic growth factors such as HGF, EGF, APRIL, syndecan-1 promotes the preferential growth and survival of neoplastic myeloma cells. Syndecan-1 and other heparan sulfate proteoglycans being coreceptors of main angiogenic growth factors: VEGF and FGF-2 contribute to neoangiogenesis in MM. Syndecan-1 and chondroitin sulfate proteoglycan serglycin and some heparan sulfate-binding cytokines are involved in osteolytic bone disease. Heparan sulfate and syndecan-1 are presented by some authors as perspective targets for therapy of MM.