Syndecan is a heparan sulfate-rich integral membrane proteoglycan. On simple epithelia a high molecular mass (160 kDa) form of syndecan acts to bind cells to extracellular matrix and binds to basic fibroblast growth factor. Syndecan is required to maintain epithelial morphology and the available data suggest that the loss of syndecan from epithelia promotes tumor formation and dissemination. Syndecan is also expressed on B lymphocytes, but its function on these cells is unknown. Its molecular mass (85 kDa) on B lymphocytes is considerably smaller than that of syndecan from simple epithelia. B lymphocytes regulate syndecan expression during their differentiation. Syndecan is found on pre-B lymphocytes in the bone marrow, absent on circulating B lymphocytes and retial matrices. Thus, syndecan is expressed only when suggesting that B lymphocytes differentiating their stage-specific adhesion. The broad, long term objective of the proposed research is to define syndecan function on myeloma cells. The hypothesis is that syndecan functions as a myeloma adhesion molecule and that changes in syndecan amount or molecular structure promote myeloma cell dissemination.
The specific aims are to: (i) define the role of syndecan in myeloma cell adhesion, (ii) assess the effect of IL-6, a potent myeloma growth factor, on syndecan expression, structure and function, (iii) determine if syndecan mediates myeloma localization and dissemination in vivo, and (iv) investigate syndecan expression on cells from patients with multiple myeloma. Syndecan function in adhesion will be assessed by measuring affinity of myeloma syndecan for matrix ligands using the affinity co-electrophoresis technique and in vitro cell binding assay. Myeloma cells grown in the presence of IL-6 will be analyzed for syndecan function and compared to cells growing without IL-6. To investigate syndecan function in myeloma cell localization and dissemination, cells will be made deficient in syndecan by antisense transfection, marked with the lac Z reporter gene, and intravenously injected into syngeneic hosts. Syndecan expression on cells in flood and bone marrow aspirates taken from myeloma patients will be examined by flow cytometry and polymerase chain reaction.
