In:
Blood, American Society of Hematology, Vol. 113, No. 19 ( 2009-05-07), p. 4614-4626
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2008-07-170464
Sprache:
Englisch
Verlag:
American Society of Hematology
Publikationsdatum:
2009
ZDB Id:
1468538-3
ZDB Id:
80069-7
