RT Journal Article
SR Electronic
T1 Thrombospondin-1 (TSP-1) and TSP-1-derived Heparin-binding Peptides Induce Promyelocytic Leukemia Cell Differentiation and Apoptosis
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 757
OP 764
VO 25
IS 2A
A1 BRUEL, ARLETTE
A1 TOUHAMI-CARRIER, MYRIEM
A1 THOMAIDIS, ANNICK
A1 LEGRAND, CHANTAL
YR 2005
UL http://ar.iiarjournals.org/content/25/2A/757.abstract
AB Thrombospondin-1 (TSP-1) is a multifunctional adhesive glycoprotein that is synthesized by several cell types and modulates cell growth and differentiation. In this study, we showed that the amount of TSP-1 secreted by two human leukemia cell lines, HL-60 and NB4, increased markedly during differentiation of these cells by all-trans retinoic acid (ATRA) (10-7 M), reaching about 100 ng/106 cells after 3 days. Addition of purified TSP-1 alone (10-9 - 5 x 10-8 M) to HL-60 or NB4 cell cultures dose-dependently inhibited cell growth and differentiation. Differently to ATRA, TSP-1-induced differentiation of HL-60 and NB4 cells occurred independently of Bcl-2 regulation, as shown by immunofluorescence and Western immunoblotting. At day 5, TSP-1 also induced promyelocytic leukemia cell apoptosis. The percentage of apoptotic cells in NB4 cultures was higher with TSP-1 (5 x 10-8 M) than with ATRA (10-7 M) (46±3% versus 19±7%, p<0.001), whereas similar levels of apoptosis (37±7% and 38±6%) were reached with both agents in HL-60 cultures. Studies performed with synthetic peptides derived from the TSP-1 sequence indicated that two heparin-binding peptides, Hep-I and GGWSHW, located within the NH2-terminal and type 1 repeats respectively, were strong inducers of apoptosis of HL-60 and NB4 cells, suggesting that cell surface heparan sulfate molecules might be involved in the apoptotic effect of TSP-1 on promyelocytic cells. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved