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Hepatocyte growth factor pathway upregulation in the bone marrow microenvironment in multiple myeloma is associated with lytic bone disease
Author(s) -
Kristensen Ida B.,
Christensen Jacob H.,
Lyng Maria B.,
Møller Michael B.,
Pedersen Lise,
Rasmussen Lars M.,
Ditzel Henrik J.,
Abildgaard Niels
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12270
Subject(s) - hepatocyte growth factor , bone marrow , multiple myeloma , monoclonal gammopathy of undetermined significance , osteoblast , cancer research , osteoclast , pathology , lytic cycle , bone disease , immunohistochemistry , medicine , chemistry , in vitro , immunology , monoclonal , monoclonal antibody , antibody , osteoporosis , biochemistry , virus , receptor
Summary Lytic 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 ( BMB s) of patients with MM and monoclonal gammopathy of undetermined significance ( MGUS ), and healthy volunteers ( HV ). BMB s ( 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 BMB s 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 SDC 1 ( S yndecan‐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 BMB s 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 .