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BMC Cancer  2010 

Growth factors in multiple myeloma: a comprehensive analysis of their expression in tumor cells and bone marrow environment using Affymetrix microarrays

DOI: 10.1186/1471-2407-10-198

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Abstract:

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).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.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.Multiple myeloma (MM) is a B cell neoplasia that affects 15 000 new patients per year in Europe and 15 000 in the United States. It is still an incurable disease with an average 5-year survival after high dose chemotherapy and autologous stem cells transplantation [1]. MM is characterized by the accumulation of a clone of malignant plasma cells in the bone marrow (BM). Hallmarks of MM are the presence of genetic abnormalities [2] and the dependence of tumor cells on their environment through cell communication signals [3]. Since the identification of IL-6 [4-6] 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 interc

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