Abstract:
: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.
journal_name
Bloodjournal_title
Bloodauthors
Sprynski AC,Hose D,Caillot L,Réme T,Shaughnessy JD Jr,Barlogie B,Seckinger A,Moreaux J,Hundemer M,Jourdan M,Meissner T,Jauch A,Mahtouk K,Kassambara A,Bertsch U,Rossi JF,Goldschmidt H,Klein Bdoi
10.1182/blood-2008-07-170464subject
Has Abstractpub_date
2009-05-07 00:00:00pages
4614-26issue
19eissn
0006-4971issn
1528-0020pii
blood-2008-07-170464journal_volume
113pub_type
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