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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4614-4626. Prepublished online as a Blood First Edition Paper on February 24, 2009; DOI 10.1182/blood-2008-07-170464. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-07-170464v1 blood-2008-07-170464v2 113/19/4614    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sprynski, A. C. Articles by Klein, B. Search for Related Content PubMed PubMed Citation Articles by Sprynski, A. C. Articles by Klein, B. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor Anne Catherine Sprynski1, Dirk Hose2,3, Laurent Caillot4, Thierry Réme1,5, John D. Shaughnessy, Jr6, Bart Barlogie6, Anja Seckinger2, Jérôme Moreaux1,5, Michael Hundemer2, Michel Jourdan1, Tobias Meißner2,3, Anna Jauch7, Karène Mahtouk1,5, Alboukadel Kassambara1, Uta Bertsch2,3, Jean François Rossi1,5,8, Hartmut Goldschmidt2,3, and Bernard Klein1,5,8 1 Inserm U847, Montpellier, France; 2 Medizinische Klinik V, Universitätsklinikum Heidelberg, Heidelberg, Germany; 3 Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany; 4 ABCell-Bio, Unit for Cellular Therapy, Centre Hospitalier Universitaire (CHU) St Eloi, Montpellier, France; 5 CHU Montpellier, Institute of Research in Biotherapy, Montpellier, France; 6 Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock; 7 Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Germany; and 8 Université Montpellier1, UFR Médecine, Montpellier, France A plethora of myeloma growth factors (MGFs) has been identified, but their relative importance and cooperation have not been determined. We investigated 5 MGFs (interleukin-6 [IL-6], insulin-like growth factor type 1 [IGF-1], hepatocyte growth factor [HGF], HB–epidermal growth factor [HB-EGF], and a proliferation-inducing ligand [APRIL]) in serum-free cultures of human myeloma cell lines (HMCLs). In CD45– HMCLs, an autocrine IGF-1 loop promoted autonomous survival whereas CD45+ HMCLs could not survive without addition of MGFs, mainly IGF-1 and IL-6. IGF-1 was the major one: its activity was abrogated by an IGF-1R inhibitor only, whereas IL-6, HGF, or HB-EGF activity was inhibited by both IGF-1R– and receptor-specific inhibition. APRIL activity was inhibited by its specific inhibitor only. Of the investigated MGFs and their receptors, only expressions of IGF-1R and IL-6R in multiple myeloma cells (MMCs) of patients delineate a group with adverse prognosis. This is mainly explained by a strong association of IGF-1R and IL-6R expression and t(4;14) translocation, but IGF-1R expression without t(4;14) can also have a poor prognosis. Thus, IGF-1–targeted therapy, eventually in combination with anti–IL-6 therapy, could be promising in a subset of patients with MMCs expressing IGF-1R. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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