Increased expression of protease-activated receptor 1 (PAR-1) in human leukemias

被引:17
作者
Veiga, Camilla de S. B.
Carneiro-Lobo, Tatiana C.
Coelho, Claudia J. B. P. [2 ]
Carvalho, Silvia M. F. [2 ]
Maia, Raquel C. [3 ]
Vasconcelos, Flavia C. [3 ]
Abdelhay, Eliana [4 ]
Mencalha, Andre L. [4 ]
Ferreira, Aline F. [5 ]
Castro, Fabiola A. [5 ]
Monteiro, Robson Q. [1 ]
机构
[1] Univ Fed Rio de Janeiro, CCS, Inst Bioquim Med, Ilha Fundao, BR-21941590 Rio De Janeiro, Brazil
[2] Inst Estadual Hematol Arthur Siqueira Cavalcanti, Lab Serv, Rio De Janeiro, Brazil
[3] INCa, CGTC, Programa Pesquisa Hematooncol Mol, Rio De Janeiro, Brazil
[4] INCa, Lab Celulas Tronco, Rio De Janeiro, Brazil
[5] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, Ribeirao Preto, SP, Brazil
关键词
Protease-activated receptor 1 (PAR-1); Thrombin; Acute myeloid leukemia; Chronic myeloid leukemia; ACUTE PROMYELOCYTIC LEUKEMIA; TISSUE FACTOR; SURVIVAL FACTOR; CANCER-CELLS; THROMBIN; ANGIOGENESIS; COAGULATION; PATHWAYS; MOTILITY; INVASION;
D O I
10.1016/j.bcmd.2010.12.005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Protease-activated receptor 1 (PAR-1) is a G-protein-coupled receptor that is overexpressed in solid tumors, being associated with several pro-tumoral responses including primary growth, invasion, metastasis and angiogenesis. Expression of PAR-1 in human leukemic cell lines is reported but the status of its expression in human leukemic patients is currently unknown. In this study we evaluated the expression pattern of PAR-1 in patients with the four main types of leukemia - chronic lymphocytic leukemia subtype B (B-CLL), acute lymphoblastic leukemia subtype B (B-ALL), acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Flow cytometry analyses show that lymphocytes from B-CLL patients express this receptor at similar levels to healthy individuals. On the other hand, it was observed a significant increase in PAR-1 expression in B-ALL lymphocytes as compared to B-CLL and healthy donors. Flow cytometric and real-time PCR demonstrated a significant increase in PAR-1 expression in granulocytes from CML patients in blast phase (CML-BP) but not in chronic phase (CML-CP) as compared to healthy donors. Finally, a significant increase in PAR-1 expression has been also observed in blasts from AML (subtypes M4 and M5) patients, as compared to monocytes or granulocytes from healthy donors. We conclude that PAR-1 might play an important biological role in aggressive leukemias and might offer additional strategies for the development of new therapies. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:230 / 234
页数:5
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