Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease

Abstract

M. (2005). Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease. Clinical Chemical Laboratory Medicine, 43 (9), 934-938.Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease AbstractMultiple myeloma is characterized by accelerated production of the proteolytic enzyme matrix metalloproteinase (MMP)-9. We hypothesized that myeloma-produced MMP-9 may influence the rate of bone turnover in a paracrine manner. Thus, we examined the correlations of MMP-9 levels, disease severity, and bone turnover rate as evaluated by markers of bone formation and resorption. Thirty-seven newly diagnosed multiple myeloma patients (nine of Durie-Salmon stage I, 12 of stage II and 16 of stage III) and 12 age-matched controls were studied. Serum MMP-9 levels were significantly higher at stage II compared to stage I (188.78"91.27 vs. 59.25"33.09 ng/mL, p-0.004). Additionally, free urine pyridinolines (F-Pyd), free urine deoxy-pyridinolines (F-Dpd) and urine N-telopeptide fragment (NTx) were elevated, their level correlating with disease stage (p-0.001, p-0.03, p-0.001, respectively), as were bone marrow infiltration and serum interleukin-6 (IL-6) levels (p-0.0001, p-0.01, respectively). MMP-9 levels were lower in patients compared with controls (p-0.001), whereas IL-6 and bone resorption marker levels were higher in patients than in controls (p-0.001 in all cases). Significant correlation was found between infiltration, MMP-9, free urine pyd, free urine dpd and NTx for each stage of the disease (p-0.03, p-0.003, p-0.002, p-0.003 and p-0.001, respectively). Levels of MMP-9 and of IL-6 in multiple myeloma correlate well with bone turnover rate and may be useful in disease evaluation. 2005/166Article in press -uncorrected proof Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease AbstractMultiple myeloma is characterized by accelerated production of the proteolytic enzyme matrix metalloproteinase (MMP)-9. We hypothesized that myeloma-produced MMP-9 may influence the rate of bone turnover in a paracrine manner. Thus, we examined the correlations of MMP-9 levels, disease severity, and bone turnover rate as evaluated by markers of bone formation and resorption.Thirty-seven newly diagnosed multiple myeloma patients (nine of Durie-Salmon stage I, 12 of stage II and 16 of stage III) and 12 age-matched controls were studied. Serum MMP-9 levels were significantly higher at stage II compared to stage I (188.78"91.27 vs. 59.25"33.09 ng/mL, p-0.004). Additionally, free urine pyridinolines (F-Pyd), free urine deoxy-pyridinolines (F-Dpd) and urine N-telopeptide fragment (NTx) were elevated, their level correlating with disease stage (p-0.001, p-0.03, p-0.001, respectively), as were bone marrow infiltration and serum interleukin-6 (IL-6) levels (p-0.0001, p-0.01, res...

Risk Factors for Multiple Myeloma: A Systematic Review of Meta-Analyses

“…35 Notably, the aggravating role of P15INK4b promoter methylation seemed rather universal, as it implicated both whites and Asians, whereas the effects of P16INK4a promoter methylation seemed confined to Asians. 35 Regarding inflammation-related molecules, a compendium of IL-6-related polymorphisms were associated with modified MM risk (rs6684439, rs2229238, rs8192284 polymorphisms in the IL-6 receptor and rs11744523 in the IL-6 signal transducer gp130), 39 in line with IL-6 as a growth factor for MM cells 79 and with the abnormally elevated serum IL-6 levels in MM patients, which may also correlate with prognosis 70,80 ; on the other hand, TNF promoter polymorphisms were not considerably associated with MM risk. 43 Finally, MTHFR C677T status seemed to modify MM risk, highlighting the role of the latter in DNA synthesis and methylation.…”

Heparanase Stimulation of Protease Expression Implicates It as a Master Regulator of the Aggressive Tumor Phenotype in Myeloma

“…In myeloma, there is evidence that MMP-9 and uPA/uPAR contribute to disease severity. High MMP-9 levels in myeloma are associated with disease recurrence and poor patient survival (52,53), and expression of uPA/uPAR is an independent factor predicting poor prognosis (54,55). Evidence suggests that MMP-9 and uPA/uPAR help promote the widespread dissemination of myeloma, a hallmark of this cancer.…”

“…*, p Ͻ 0.01 versus heparanase high cells. (52,53). High levels of soluble uPAR are associated with poor prognosis and bone disease in myeloma patients (55), and interactions between osteoclasts and myeloma cells stimulate expression of MMP-9 and uPA possibly creating a microenvironment conducive to bone degradation (62).…”

Physiological matrix metalloproteinase (MMP) concentrations: comparison of serum and plasma specimens

“…For disease states characterized by cellular inflammatory responses, such as multiple sclerosis (5,6) and coronary artery disease (7)(8)(9), or malignant proliferation of inflammatory cell types such as multiple myeloma (10,11) and chronic lymphocytic leukemia (12,13), differences in serum measurements of MMPs have been detected and may provide a marker of pertinent intracellular protease activity. Alternatively, elevated concentrations of MMPs in serum might emanate from a circulating cell-type associated with a pathological condition.…”