Hepatocyte growth factor pathway upregulation in the bone marrow microenvironment in multiple myeloma is associated with lytic bone disease. (22nd February 2013)

• Record Type: Journal Article
• Authors: Kristensen, Ida B.; Christensen, Jacob H.; Lyng, Maria B.; Møller, Michael B.; Pedersen, Lise; Rasmussen, Lars M.; Ditzel, Henrik J.; Abildgaard, Niels
• Is Part Of: British journal of haematology. Volume 161:Number 3(2013:May)
• Page Start: 373
• Page End: 382
• Publication Date: 2013-02-22
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12270
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" xml:lang="en" id="bjh12270-abs-0001"> <title>Summary</title> <p>Lytic bone disease (LBD) in multiple myeloma (MM) is caused by osteoclast hyperactivation and osteoblast inhibition. Based on <italic>in vitro</italic> studies, the hepatocyte growth factor (HGF) pathway is thought to be central in osteoblast inhibition. We evaluated the gene expression of the HGF pathway <italic>in vivo</italic> using bone marrow biopsies (BMBs) of patients with MM and monoclonal gammopathy of undetermined significance (MGUS), and healthy volunteers (HV). BMBs (<italic>N</italic> = 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 <italic>HGF</italic>, <italic>SDC1</italic>, and <italic>MET</italic> in BMBs were significantly altered in MM <italic>versus </italic>HV and MGUS, and <italic>HGF</italic> and <italic>MET</italic> 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 <italic>versus</italic> 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.</p> </abstract>