Guest guest Posted September 11, 2006 Report Share Posted September 11, 2006 Biochem Biophys Res Commun. 2006 Aug 30; [Epub ahead of print] Malignant hematopoietic cells induce an increased expression of VEGFR- 1 and VEGFR-3 on bone marrow endothelial cells via AKT and mTOR signalling pathways. Mirshahi P, Toprak SK, Faussat AM, Dubrulle S, Marie JP, Soria C, Soria J, Mirshahi M. INSERM, UMR736, IFR 58, Universite Pierre et Marie Curie, 75006 Paris, France; Laboratoire Difema, Faculte de Medecine et de Pharmacie, 76000 Rouen, France. Angiogenesis plays a significant role in a variety of malignant hematologic diseases, and it is recognized that it has prognostic value. However, the cellular mechanisms by which malignant hematologic cells induce angiogenesis are not well understood. In order to investigate the role of cells from B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma (MM) in angiogenesis on human bone marrow endothelial cells (HBMEC), we analyzed the impact of factors secreted by B-CLL cells and by MM cells on HBMEC capillary tube formation on matrigel. It was found that, in addition to the secretion of angiogenic factors VEGF and b-FGF by B-CLL and MM cells, MM cells (but not B-CLL cells) induced a dramatic increase in expression of VEGFR-1 and VEGFR-3 on human bone marrow endothelial cells (HBMEC). It would seem that this increase in VEGFR-3 occurred via the ERK and mTOR pathways, since their respective inhibitors U0126, LY294002 or rapamycin were responsible for a decrease of VEGFR-3. In response to MM cells-increased VEGF receptors on HBMEC, endothelial cell migration was enhanced in a wound artificially produced in a semi-confluent HBMEC culture, a phenomenon which was also down-regulated by the same inhibitors that reversed the increase in VEGF receptors. The present study suggests that, in addition to the classic angiogenic pathway, another mechanism related to an increased expression of VEGFRs on HBMEC might exist in malignant hematopoietic angiogenesis. PMID: 16959214 [PubMed - as supplied by publisher] Quote Link to comment Share on other sites More sharing options...
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