PMID- 24716444
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140416
LR  - 20211021
IS  - 2050-7771 (Print)
IS  - 2050-7771 (Electronic)
IS  - 2050-7771 (Linking)
VI  - 2
IP  - 1
DP  - 2014 Apr 9
TI  - Identification of the source of elevated hepatocyte growth factor levels in 
      multiple myeloma patients.
PG  - 8
LID - 10.1186/2050-7771-2-8 [doi]
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is a pleiotropic cytokine which can 
      lead to cancer cell proliferation, migration and metastasis. In multiple myeloma 
      (MM) patients it is an abundant component of the bone marrow. HGF levels are 
      elevated in 50% of patients and associated with poor prognosis. Here we aim to 
      investigate its source in myeloma. METHODS: HGF mRNA levels in bone marrow core 
      biopsies from healthy individuals and myeloma patients were quantified by 
      real-time PCR. HGF gene expression profiling in CD138+ cells isolated from bone 
      marrow aspirates of healthy individuals and MM patients was performed by 
      microarray analysis. HGF protein concentrations present in peripheral blood of MM 
      patients were measured by enzyme-linked immunosorbent assay (ELISA). Cytogenetic 
      status of CD138+ cells was determined by fluorescence in situ hybridization 
      (FISH) and DNA sequencing of the HGF gene promoter. HGF secretion in co-cultures 
      of human myeloma cell lines and bone marrow stromal cells was measured by ELISA. 
      RESULTS: HGF gene expression profiling in both bone marrow core biopsies and 
      CD138+ cells showed elevated HGF mRNA levels in myeloma patients. HGF mRNA levels 
      in biopsies and in myeloma cells correlated. Quantification of HGF protein levels 
      in serum also correlated with HGF mRNA levels in CD138+ cells from corresponding 
      patients. Cytogenetic analysis showed myeloma cell clones with HGF copy numbers 
      between 1 and 3 copies. There was no correlation between HGF copy number and HGF 
      mRNA levels. Co-cultivation of the human myeloma cell lines ANBL-6 and JJN3 with 
      bone marrow stromal cells or the HS-5 cell line resulted in a significant 
      increase in secreted HGF. CONCLUSIONS: We here show that in myeloma patients HGF 
      is primarily produced by malignant plasma cells, and that HGF production by these 
      cells might be supported by the bone marrow microenvironment. Considering the 
      fact that elevated HGF serum and plasma levels predict poor prognosis, these 
      findings are of particular importance for patients harbouring a myeloma clone 
      which produces large amounts of HGF.
FAU - Rampa, Christoph
AU  - Rampa C
AD  - The K. G. Jebsen Center for Myeloma Research and Department of Cancer Research 
      and Molecular Medicine, Norwegian University of Science and Technology, 
      Trondheim, Norway.
FAU - Tian, Erming
AU  - Tian E
AD  - The Donna D. and Donald M. Lambert Laboratory of Myeloma Genetics, Myeloma 
      Institute for Research and Therapy, University of Arkansas for Medical Sciences, 
      Little Rock, Arkansas, USA.
FAU - Vatsveen, Thea Kristin
AU  - Vatsveen TK
AD  - The K. G. Jebsen Center for Myeloma Research and Department of Cancer Research 
      and Molecular Medicine, Norwegian University of Science and Technology, 
      Trondheim, Norway.
FAU - Buene, Glenn
AU  - Buene G
AD  - The K. G. Jebsen Center for Myeloma Research and Department of Cancer Research 
      and Molecular Medicine, Norwegian University of Science and Technology, 
      Trondheim, Norway.
FAU - Slordahl, Tobias Schmidt
AU  - Slordahl TS
AD  - The K. G. Jebsen Center for Myeloma Research and Department of Cancer Research 
      and Molecular Medicine, Norwegian University of Science and Technology, 
      Trondheim, Norway.
FAU - Borset, Magne
AU  - Borset M
AD  - The K. G. Jebsen Center for Myeloma Research and Department of Cancer Research 
      and Molecular Medicine, Norwegian University of Science and Technology, 
      Trondheim, Norway.
FAU - Waage, Anders
AU  - Waage A
AD  - The K. G. Jebsen Center for Myeloma Research and Department of Cancer Research 
      and Molecular Medicine, Norwegian University of Science and Technology, 
      Trondheim, Norway.
AD  - Section of Hematology, St. Olavs University Hospital, Trondheim, Norway.
FAU - Sundan, Anders
AU  - Sundan A
AD  - The K. G. Jebsen Center for Myeloma Research and Department of Cancer Research 
      and Molecular Medicine, Norwegian University of Science and Technology, 
      Trondheim, Norway.
LA  - eng
PT  - Journal Article
DEP - 20140409
PL  - England
TA  - Biomark Res
JT  - Biomarker research
JID - 101607860
PMC - PMC4022385
EDAT- 2014/04/11 06:00
MHDA- 2014/04/11 06:01
PMCR- 2014/04/09
CRDT- 2014/04/11 06:00
PHST- 2014/01/16 00:00 [received]
PHST- 2014/03/29 00:00 [accepted]
PHST- 2014/04/11 06:00 [entrez]
PHST- 2014/04/11 06:00 [pubmed]
PHST- 2014/04/11 06:01 [medline]
PHST- 2014/04/09 00:00 [pmc-release]
AID - 2050-7771-2-8 [pii]
AID - 10.1186/2050-7771-2-8 [doi]
PST - epublish
SO  - Biomark Res. 2014 Apr 9;2(1):8. doi: 10.1186/2050-7771-2-8.