Elevated serum concentration of hepatocyte growth factor in patients with multiple myeloma: correlation with markers of disease activity

Am J Hematol. 2003 Apr;72(4):229-33. doi: 10.1002/ajh.10304.


Hepatocyte growth factor (HGF) has been shown to be involved in angiogenesis, epithelial cell proliferation, and osteoclast activation. HGF and its receptor are expressed on myeloma cell lines and could be involved in the pathogenesis of bone destruction in multiple myeloma (MM). The aim of this study was to examine serum levels of HGF in untreated MM patients and its correlation with bone turnover indices and markers of disease activity. Forty-seven newly diagnosed MM patients and 25 controls were included: 12 patients were of stage I, 13 of stage II, and 22 of stage III (Durie-Salmon classification). Bone lesions were scored from 0 to 3, according to X-ray findings. Serum osteocalcin (OC), interleukin-6 (IL-6), TNF-alpha, beta(2)-microglobulin (beta(2)M), CRP, calcium, and 24-hr urine N-telopeptide cross-links of collagen breakdown (NTx) were determined. HGF levels were significantly higher at stage III compared to stages II and I (medians: 1,990.4 vs. 1,743.8 and 1,432.4 pg/mL, respectively, P < 0.05). Similarly, NTx, IL-6, TNF-alpha, CRP, beta(2)M, and calcium increased significantly with advancing stage (P < 0.01). OC was higher at stage I in comparison to stages II and III (P < 0.01). All parameters were significantly higher in patients than controls. HGF showed a strong correlation with IL-6 and TNF-alpha and less with beta(2)M, CRP, NTx, and OC. We conclude that serum HGF levels are increased in advanced stages of MM disease and extended bone lesions. HGF correlates with IL-6 and TNF-alpha, which are cytokines involved in osteoclast stimulation in MM. However, an independent association of HGF with bone turnover markers was not shown in this study, thus its role in MM bone disease needs to be further clarified.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism
  • C-Reactive Protein / analysis
  • Calcium / blood
  • Collagen / urine
  • Collagen Type I
  • Female
  • Hepatocyte Growth Factor / blood*
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Multiple Myeloma / blood*
  • Multiple Myeloma / complications
  • Multiple Myeloma / pathology
  • Neoplasm Proteins / blood*
  • Neoplasm Proteins / metabolism
  • Osteocalcin / blood
  • Osteoclasts / metabolism
  • Osteolysis / blood*
  • Osteolysis / etiology
  • Peptides / urine
  • Tumor Necrosis Factor-alpha / analysis
  • beta 2-Microglobulin / blood


  • Biomarkers
  • Biomarkers, Tumor
  • Collagen Type I
  • Interleukin-6
  • Neoplasm Proteins
  • Peptides
  • Tumor Necrosis Factor-alpha
  • beta 2-Microglobulin
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Hepatocyte Growth Factor
  • Collagen
  • C-Reactive Protein
  • Calcium