Syndecan-1 in Multiple Myeloma: Relationship to Conventional Prognostic Factors

Abstract

Syndecan-1 (CD138) mediates myeloma cell adhesion, and loss of syndecan-1 from the cell surface may contribute to myeloma cell proliferation and dissemination and influence the prognosis in patients with multiple myeloma (MM). In order to test this hypothesis, we have evaluated syndecan-1 expression on the surface of malignant plasma cells and soluble forms of syndecan-1 in the serum of 25 newly diagnosed MM patients by flow cytometry and immunosorbent assay. Soluble syndecan-1 levels were significantly higher in MM as compared to controls (P<0.001). Cellular and soluble syndecan-1 was significantly inversely correlated (r=-0.89, P<0.001). The soluble syndecan-1 was significantly higher in non- responders to chemotherapy when compared to responders (P<0.01), and in non- survivors as compared to survivors (P<0.001). In contrast, cellular syndecan-1 expression was significantly lower in non- responders when compared to responders (P<0.01), and in non- survivors as compared to survivors (P<0.05). The levels of soluble syndecan-1 increased from stage I through stage II to stage III, whereas cellular syndecan-1 expression were decreased from high levels in stage III down to a low in stage I, with a statistically significant difference (P<0.01, P<0.05, respectively). There was a significant positive correlation between soluble syndecan-1 and plasma cell count (r=0.079, P<0.001), beta2 microglobulin (r=0.85, P<0.001), serum creatinine (r=0.84, P<0.001), C-reactive protein (r=0.082, P<0.001), alkaline phosphatase (r=0.58, P<0.05) and serum calcium (r=0.77, P<0.01) and a negative correlation with hemoglobin level (r=-0.78, P<0.01), platelets count (r=-0.82, P<0.01) and Albumin level (r=-0.64, P<0.01). Cox regression analysis using soluble syndecan-1 at mean-2SD of the controls could correctly classify patient outcome in 84.0%. The addition of beta2 microglobulin to soluble syndecan-1 increased the predictability of the patients' outcome to 96.7%. We conclude that soluble syndecan-1 levels are negatively correlated to the cellular form and that high levels of soluble syndecan-1 and lower expression of cellular syndecan-1 at diagnosis are negative prognostic factors. Assessment of soluble syndecan-1 and beta2 microglobulin at diagnosis is an independent prognostic system for MM.

EBV-Positive Plasmacytoma of the Submandibular Gland—Report of a Rare Case with Molecular Genetic Characterization

“…Proposed mechanisms for weak/absent CD138 expression in malignant plasma cells include apoptosis (unlikely in our patient) [7] and increased shedding from the cell surface [6]. The clinical relevance of weak/absent CD138 expression is not established, but various studies suggest that plasma cell tumors with weak/ absent CD138 expression exhibit more aggressive behavior [6,8] and may be less chemosensitive [8].…”

Fibroblast growth factor-2 (FGF2) and syndecan-1 (SDC1) are potential biomarkers for putative circulating CD15+/CD30+ cells in poor outcome Hodgkin lymphoma patients

“…Although FGF2 may not always mediate SDC1 expression in cancers, SDC1 overexpression, at either a tissue or serum level, has been reported for multiple tumor types including solid tumors [42-44], lymphomas, and in a number of lymphoproliferative disorders [29,30,45-47]. In some instances, SDC1 overexpression is an adverse indicator for both solid and hematological malignancies [43,44,48-50]. High levels of FGF2 and SDC1 in the same patient have important clinical implications.…”

Syndecan-2 Affects the Basal and Chemotherapy-Induced Apoptosis in Osteosarcoma

“…They modulate the binding and availability of factors, thereby inducing downstream signaling pathways that control cell adhesion, migration, differentiation, and proliferation. Both tumor suppressor and tumor growth promoter activities have been reported for syndecans depending on the type of cancer (7)(8)(9). Syndecan-2 cooperates with integrins in lung carcinoma cells (10) to induce adhesion and was found associated with an antimetastatic effect (11).…”