Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays.
BACKGROUND
Multiple myeloma (MM) is characterized by a strong dependence of the tumor cells on their microenvironment, which produces growth factors supporting survival and proliferation of myeloma cells (MMC). In the past few years, many myeloma growth factors (MGF) have been described in the literature. However, their relative importance and the nature of the cells producing MGF remain unidentified for many of them.


METHODS
We have analysed the expression of 51 MGF and 36 MGF receptors (MGFR) using Affymetrix microarrays throughout normal plasma cell differentiation, in MMC and in cells from the bone marrow (BM) microenvironment (CD14, CD3, polymorphonuclear neutrophils, stromal cells and osteoclasts).


RESULTS
4/51 MGF and 9/36 MGF-receptors genes were significantly overexpressed in plasmablasts (PPC) and BM plasma cell (BMPC) compared to B cells whereas 11 MGF and 11 MGFR genes were overexpressed in BMPC compared to PPC. 3 MGF genes (AREG, NRG3, Wnt5A) and none of the receptors were significantly overexpressed in MMC versus BMPC. Furthermore, 3/51 MGF genes were overexpressed in MMC compared to the the BM microenvironment whereas 22/51 MGF genes were overexpressed in one environment subpopulation compared to MMC.


CONCLUSIONS
Two major messages arise from this analysis 1) The majority of MGF genes is expressed by the bone marrow environment. 2) Several MGF and their receptors are overexpressed throughout normal plasma cell differentiation. This study provides an extensive and comparative analysis of MGF expression in plasma cell differentiation and in MM and gives new insights in the understanding of intercellular communication signals in MM.
Mahtouk
Karène
K
INSERM, U847, Montpellier, F-34197 France.
Moreaux
Jérôme
J
Hose
Dirk
D
Rème
Thierry
T
Meissner
Tobias
T
Jourdan
Michel
M
Rossi
Jean François
JF
Pals
Steven T
ST
Goldschmidt
Hartmut
H
Klein
Bernard
B
D001854:Bone Marrow Cells / Q000737:chemistry* / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000737:chemistry* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis*; D017978:Receptors, Growth Factor / Q000235:genetics; D015854:Up-Regulation
D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor
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