Abstract
BackgroundMultiple 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.MethodsWe 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).Results4/51 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.ConclusionsTwo 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.
Highlights
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)
2) Several myeloma growth factors (MGF) and their receptors are overexpressed throughout normal plasma cell differentiation
Affymetrix microarrays to investigate Myeloma Growth Factor (MGF) expression in bone marrow (BM) subpopulations Based on the literature data, we have listed 32 growth factors that have already been described as growth factors for MMC (Table A1A)
Summary
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). Since the identification of IL-6 [4,5,6] and IGF-1 [7] as major myeloma growth factor (MGF) in 1988 and 1996, respectively, the identification of new autocrine and/or paracrine MGF has been constantly increasing, making it difficult to understand intercellular communication signals in MM (see [3,8] for review and Table A1A). This is a major question, in particular with the aim to design novel targeted therapies for MM
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