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c-Met signaling promotes IL-6-induced myeloma cell proliferation.

Abstract：

OBJECTIVES:Hepatocyte growth factor (HGF) is a constituent of the myeloma microenvironment and is elevated in sera from myeloma patients compared to healthy individuals. Increased levels of serum HGF predict a poor prognosis. It has previously been shown by us and others HGF can act as a growth factor to myeloma cells in vitro although these effects have been moderate. We therefore wanted to investigate if HGF could influence the effects of interleukin (IL)-6. METHODS:Myeloma cell lines and primary samples were tested for the combined effects of IL-6 and HGF in inducing DNA synthesis and migration. Expression levels of c-Met protein were analysed by Western blotting and flow cytometry. Signaling pathways were examined by Western blotting using phosphospecific antibodies and a Ras-GTP pull down assay. RESULTS:HGF potentiated IL-6-induced growth in human myeloma cell lines and in purified primary myeloma cells. There was also cooperation between HGF and IL-6 in induction of migration. There seemed to be two explanations for this synergy. IL-6-treatment increased the expression of c-Met making cells HGF responsive, and IL-6 was dependent on c-Met signaling in activating both Ras and p44/42 MAPK by a mechanism involving the tyrosine phosphatase Shp2. CONCLUSIONS:The results indicate that besides from being a myeloma growth factor alone, HGF can also potentiate the effects of IL-6 in myeloma proliferation and migration. Thus, c-Met signaling could be a target for therapy of multiple myeloma.

journal_name

Eur J Haematol

journal_title

European journal of haematology

authors

Hov H,Tian E,Holien T,Holt RU,Våtsveen TK,Fagerli UM,Waage A,Børset M,Sundan A

doi

10.1111/j.1600-0609.2009.01212.x

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

277-87

issue

4

eissn

0902-4441

issn

1600-0609

pii

EJH1212

journal_volume

82

pub_type

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