Autocrine/paracrine involvement of insulin-like growth factor-I and its receptor in chronic lymphocytic leukaemia.
Chronic lymphocytic leukaemia (CLL) is characterized by the accumulation of long-lived B lymphocytes blocked in G(0/1) by impaired apoptosis. As insulin-like growth factor-I (IGF-I) is known for its antiapoptotic effects in different cell types, we investigated whether IGF-I and its receptor (IGF-IR) participate in autocrine/paracrine loops affecting the survival of CLL cells. IGF-IR protein and mRNA was present in CLL cells in 44% and 59% of patients respectively. IGF-IR expression in CLL patients was positively correlated with the expression of the antiapoptotic protein Bcl-2 and was involved in CLL cell survival in vitro. Serum IGF-I was elevated in CLL patients, but growth hormone (GH) was normal. CLL cells expressed IGF-I mRNA and secreted the growth factor in vitro. Therefore, local production of IGF-I can account for the increased levels of serum IGF-I, independently of GH, and may be related to autocrine/paracrine control of lymphocyte survival acting at IGF-IR. This is the first demonstration of IGF-IR expression in a subgroup of CLL patients and of its antiapoptotic effects in vitro, highlighting the importance of this growth factor receptor as a possible therapeutic target in CLL.
Instituto de Biología y Medicina Experimental CONICET, Buenos Aires, Argentina. rschilla@dna.uba.ar
Roxana
R
Schillaci
Adriana
A
Galeano
Damasia
D
Becu-Villalobos
Olga
O
Spinelli
Sandra
S
Sapia
Raimundo F
RF
Bezares
D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D017209:Apoptosis; D019898:Autocrine Communication; D001402:B-Lymphocytes / Q000737:chemistry / Q000378:metabolism*; D016022:Case-Control Studies; D017077:Culture Media, Conditioned / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1