Macrophage inflammatory protein‐1 alpha is produced by human multiple myeloma (MM) cells and its expression correlates with bone lesions in patients with MM

Uneda, Shima; Hata, Hiroyuki; Matsuno, Fumihiko; Harada, Naoko; Mitsuya, Yumi; Kawano, Fumio; Mitsuya, Hiroaki

doi:10.1046/j.1365-2141.2003.04040.x

Cited by 80 publications

(63 citation statements)

References 10 publications

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“…PTH does not have a primary role in MM bone disease. PTH levels of MM patients have been found to be similar to those in healthy controls, however, a few hypercalcemic MM patients were reported to have had high levels of PTH related peptide, which may cause hypercalcemia [35][36][37].…”

Section: Discussionmentioning

confidence: 98%

Biochemical markers of bone turnover in diagnosis of myeloma bone disease

Dizdar¹,

Barışta²,

Kalyoncu³

et al. 2006

American J Hematol

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This study was designed to explore the value of markers of bone turnover, macrophage inflammatory protein-1a (MIP-1a), and osteopontin (OPN) in the diagnosis of myeloma bone disease. Twenty-five patients with newly diagnosed and untreated multiple myeloma (MM), and 22 age-, sex-, and bone mineral density-matched control subjects were enrolled. Levels of MIP-1a, OPN, carboxy-terminal telopeptide of Type-1 collagen (C-telopeptide or Ctx), deoxypyridinoline (DPD), Type-1 collagen propeptide (T1Pro), and bone-specific alkaline phosphatase (BALP) were assessed in both groups. Twenty-two of the patients had bone involvement documented by skeletal surveys and lumbar spinal magnetic resonance imaging. Levels of serum Ctx, OPN, MIP-1a, and urine DPD were significantly higher in MM patients with bone disease than in controls (P < 0.01). Serum Ctx levels were elevated in 90.9% of patients with MM and 40.9% of controls (P < 0.001). Urine DPD levels were elevated in 90.4% of the patients and 31.8% of the controls (P < 0.001). The serum OPN and MIP-1a levels of the patients were significantly correlated with b2-microglobulin and lactate dehydrogenase levels (P < 0.05). Our study indicates that Ctx and DPD are sensitive markers of bone disease in MM, and higher than normal values suggest presence of bone disease rather than benign osteoporosis in MM. The utility of OPN and MIP-1a needs to be further investigated. Am. J. Hematol. 82:185-191, 2007. V V C 2006 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 98%

Biochemical markers of bone turnover in diagnosis of myeloma bone disease

Dizdar¹,

Barışta²,

Kalyoncu³

et al. 2006

American J Hematol

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“…It strongly correlates with osteolytic burden in MM [57][58][59]. Indeed, CCL3 by binding two receptors, CCR1 and CCR5, potently stimulates OC differentiation mediating the fusion of precursor cells into active mature OCs and upregulating RANKL expression by OBs [60][61][62].…”

Section: Pathogenesis Of Osteoblast Inhibition In MMmentioning

confidence: 99%

Bone Anabolic Agents for the Treatment of Multiple Myeloma

Vallet

2011

Cancer Microenvironment

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The majority of patients with multiple myeloma develop bone osteolytic lesions, which may lead to severe complications, including pain and fractures. The pathogenesis of bone disease depends on uncoupled bone remodeling, characterized by increased bone resorption due to upregulation of osteoclast activity and decreased bone formation due to osteoblast inhibition. In myeloma, impaired osteoblast differentiation and increased apoptosis have been described. Responsible for these effects are integrin-mediated adhesion to tumor cells and soluble factors, including WNT antagonists, BMP2 inhibitors and numerous cytokines. Based on the evidence of osteoblast suppression in myeloma, bone anabolic agents have been developed and are currently undergoing clinical evaluation. Due to bidirectional inhibitory effects characterizing tumor cells and osteoblasts interactions, agents targeting osteoblasts are expected to reduce tumor burden along with improvement of bone health. This review summarizes the current knowledge on osteoblast inhibition in myeloma and provides an overview on the clinical grade agents with bone anabolic properties, which represent new promising therapeutic strategies in myeloma.

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“…Recently, the genes that encode for macrophage inflammatory protein-1 alpha (MIP-1a) and -beta (MIP-1b) (CCL3 and CCL4 respectively) have been identified as candidate genes for osteclastogenic factors (Choi et al, 2000;Han et al, 2001;Abe et al, 2002) and studies have shown that the majority of MM cells from patients and MM cell lines secrete MIP-1a and MIP1b (Abe et al, 2002;Uneda et al, 2003;Hashimoto et al, 2004) and serum MIP-1a levels correlate with the extent of OBD and survival (Terpos et al, 2005). These factors enhance osteoclast formation by binding to their cognate receptor, CCR5, on osteoclast precursors.…”

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confidence: 99%

Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis

et al. 2007

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SummaryOsteolytic bone disease (OBD) in multiple myeloma (MM) is caused by interactions between MM cells and the bone marrow microenvironment and is characterized by increased osteoclastic bone resorption and decreased osteoblastic bone formation. Recently, the role of osteoblast inhibition has come into focus, especially the possible role of overexpression of DKK1, an inhibitor of the Wnt signalling pathway. Further, CKS2, PSME2 and DHFR have also been reported as candidate genes for OBD. We studied the gene expression by quantitative reverse transcription polymerase chain reaction of TNFSF11 (RANKL), TNFSF11A (RANK), TNFRSF11B (OPG), CCL3 (MIP1A), CCL4 (MIP1B), PTHR1 (PTHrp), DKK1, CKS2, PSME2 and DHFR in purified, immunophenotypic FACS‐sorted plasma cells from 171 newly diagnosed MM patients, 20 patients with monoclonal gammopathy of undetermined significance and 12 controls. The gene expressions of the analysed genes were correlated with radiographically assessed OBD. Only overexpression of DKK1 was correlated to the degree of OBD. Myeloma cells did not express TNFSF11A, TNFSF11, or TNFRSF11B, and very rarely expressed CCL3 and PTHR11. CCL4, CKS2, PSME2 and DHFR were variably expressed, but the expression of these genes showed no correlation with OBD. In contrast, loss of PSME2 expression in MM plasma cells was significantly correlated with OBD.

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Macrophage inflammatory protein‐1 alpha is produced by human multiple myeloma (MM) cells and its expression correlates with bone lesions in patients with MM

Cited by 80 publications

References 10 publications

Biochemical markers of bone turnover in diagnosis of myeloma bone disease

Biochemical markers of bone turnover in diagnosis of myeloma bone disease

Bone Anabolic Agents for the Treatment of Multiple Myeloma

Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis

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