The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor. - Archive ouverte HAL Access content directly
Journal Articles Blood Year : 2009

The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor.

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Laurent Caillot
  • Function : Author
Jérôme Moreaux

Abstract

A plethora of myeloma growth factors (MGF) has been identified, but their relative importance and cooperation has not been determined. We investigated 5 well-documented MGF (IL-6, IGF-1, HGF, HB-EGF, APRIL) in serum-free cultures of human myeloma cell lines (HMCLs). In all of 3 CD45(-) HMCLs, an autocrine IGF-1 loop promoted autonomous survival. To the contrary, all 5 CD45(+) HMCLs could not survive and required addition of either IL-6 (5/5), IGF-1 (4/5), HGF (1/5), HB-EGF (1/5) or APRIL (1/5). IGF-1 was the major MGF since 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 MGF and their receptors, only expressions of IGF-1R and IL-6R in myeloma cells (MMC) 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 in MMC, 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 MMC expressing IGF-1R.
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Dates and versions

inserm-00367812 , version 1 (01-04-2009)

Identifiers

Cite

Anne Catherine Sprynski, Dirk Hose, Laurent Caillot, Thierry Rème, John D. Shaughnessy Jr, et al.. The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor.: IGF-1 is the major growth factor on myeloma. Blood, 2009, 113 (19), pp.4614-4626. ⟨10.1182/blood-2008-07-170464⟩. ⟨inserm-00367812⟩
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