Elevated Serum Concentrations of Hepatocyte Growth Factor in Patients With Multiple Myeloma

Seidel, Carina; Børset, Magne; Turesson, Ingemar; Abildgaard, Niels; Sundan, Anders; Waage, Anders

doi:10.1182/blood.v91.3.806

Cited by 178 publications

(64 citation statements)

References 36 publications

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“…Both the expression of HGF in malignant tumours and circulating levels of HGF in cancer patients are frequently increased [34, 35]. In primary breast cancer and multiple myeloma, high circulating HGF levels predict an unfavourable prognosis [35, 36]. These findings should be considered when using heparin in patients with malignancies.…”

Section: Discussionmentioning

confidence: 99%

Heparin‐mediated selective release of hepatocyte growth factor in humans

Salbach

Brückmann

Turovets

et al. 2000

Brit J Clinical Pharma

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Aims The aim of this investigation was to compare the effects of standard (S) with low molecular weight (LMW) heparin on circulating levels of heparin‐binding growth factors (HBGF), known to have angiogenic properties in humans. Methods In two consecutive trials 18 healthy male voluteers were studied on three separate occasions, following a placebo‐controlled crossover design. Subjects were randomised to receive either S‐heparin or LMW heparin or placebo. Heparins were administered either by intravenous (i.v.) or subcutaneous (s.c.) injection and saline placebo by i.v. injection. Serum concentrations of hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF) were measured before and up to 24 h after injection. Results Administration of i.v. S‐or LMW‐heparin (50 IU kg−1) resulted in rapid, highly significant (47 fold for S, 30.9 fold for LMW) increases in HGF serum values, reaching maxima of 10.51 ± 1.65 ng ml−1 (S) and 8.28 ± 1.04 ng ml−1 (LMW), respectively, 10 min after drug application. S.c. injection of S‐heparin or LMW heparin resulted in 4.1 and 5.4 fold increases in HGF serum values, respectively. Both agents showed no effects on circulating VEGF or bFGF levels, independent of the route of administration. Conclusions Circulating HGF levels were selectively increased in response to pharmacological doses of two, widely used heparin preparations. This may, in part, explain some of the biological effects of heparin separate from its anticoagulant properties. By this mechanism, the systemic administration of heparin may facilitate collateral vessel formation in various clinical settings of tissue ischaemia.

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Section: Discussionmentioning

confidence: 99%

Heparin‐mediated selective release of hepatocyte growth factor in humans

Salbach

Brückmann

Turovets

et al. 2000

Brit J Clinical Pharma

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“…Full length HGF (consisting of four kringle domains) has been found to be produced by MM PCs , and HGF is among the most upregulated genes in MM (Zhan et al , ). Elevated serum levels of HGF have been shown to be an adverse prognostic factor (Seidel et al , ; Sezer et al , ), as has also recently been shown of MM PC expression of the HGF receptor c‐Met ( MET ; Rocci et al , ). Functionally, HGF inhibits osteoblastogenesis in vitro (Standal et al , ) and promotes migration of MM PCs (Holt et al , ).…”

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confidence: 99%

Hepatocyte growth factor pathway upregulation in the bone marrow microenvironment in multiple myeloma is associated with lytic bone disease

et al. 2013

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SummaryLytic bone disease (LBD) in multiple myeloma (MM) is caused by osteoclast hyperactivation and osteoblast inhibition. Based on in vitro studies, the hepatocyte growth factor (HGF) pathway is thought to be central in osteoblast inhibition. We evaluated the gene expression of the HGF pathway in vivo using bone marrow biopsies (BMBs) of patients with MM and monoclonal gammopathy of undetermined significance (MGUS), and healthy volunteers (HV). BMBs (N = 110) obtained at diagnosis were snap-frozen and used to evaluate gene expression by quantitative reverse transcription polymerase chain reaction. LBD was evaluated using standard radiographs. Enzyme-linked immunosorbent assay (ELISA) was performed on matched bone marrow plasma and immunohistochemistry on matched formalin-fixed paraffin-embedded biopsies. Gene expression of HGF, SDC1, and MET in BMBs were significantly altered in MM versus HV and MGUS, and HGF and MET correlated with the extent of LBD. A significant correlation between gene and protein expression levels was observed for SDC1 (Syndecan-1) and HGF. The HGF bone marrow plasma level was significantly lower in MM patients with no/limited versus advanced LBD. Our novel approach using snap-frozen BMBs seems generally applicable because it allows evaluation of gene expression independent of the extent of MM plasma-cell infiltration. Our study highlights the importance of the HGF pathway in MM LBD.

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“…HGF is produced and secreted by malignant plasma cells as well as bone marrow stromal cells and has prognostic impact in multiple myeloma . The HGF receptor cMet is expressed by endothelial cells, and HGF/cMET signalling activates multiple intracellular pathways involved in endothelial cell adhesion and migration as well as branching morphogenesis .…”

Section: Discussionmentioning

confidence: 99%