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.