| Texto completo | |
| Autor(es): |
de Vasconcellos, Jaira Ferreira
[1, 2]
;
Albertoni Laranjeira, Angelo Brunelli
[2]
;
Tonin Zanchin, Nilson Ivo
[3]
;
Otubo, Rosemary
[2]
;
Vaz, Thais Haline
[3]
;
Cardoso, Angelo Almeida
[4]
;
Brandalise, Silvia Regina
[2, 5]
;
Yunes, Jose Andres
[2]
Número total de Autores: 8
|
| Afiliação do(s) autor(es): | [1] Univ Estadual Campinas, Fac Med Sci, Dept Med Genet, Campinas, SP - Brazil
[2] Ctr Infantil Boldrini, Lab Biol Mol, BR-13083210 Campinas, SP - Brazil
[3] Ctr Struct Mol Biol, Brazilian Synchrotron Light Lab, Campinas, SP - Brazil
[4] Indiana Univ Sch Med, IU Simon Canc Ctr, Indianapolis, IN - USA
[5] Univ Estadual Campinas, Fac Med Sci, Dept Pediat, Campinas, SP - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | PEDIATRIC BLOOD & CANCER; v. 56, n. 4, p. 568-577, APR 2011. |
| Citações Web of Science: | 24 |
| Resumo | |
Background. The interactions of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells have a positive impact on leukemia cell survival. In the present study, we proposed to identify and investigate the role of molecules critically involved in leukemia-microenvironment crosstalk. Procedure. Gene expression profiling analyses of BM mesenchymal stem cells (BMMSC) were performed following stimulation by ALL cells. CCL2 and IL-8 plasma levels were evaluated from, ALL patients and controls. Expression of the CCL2 and IL-8 receptors in ALL was determined by RT-PCR. The biological effects of CCL2, IL-8 or its neutralizing antibodies in primary precursor-B ALL and BMMSC cells were evaluated using in vitro assays. Results. Leukemia stimulation of BMMSC upregulated the expression of several inflammatory chemokines, including CCL2 and IL-8. The BM plasma levels of CCL2 and IL-8 in children at diagnosis were significantly higher than in healthy controls (P < 0.00)). Functional studies revealed that CCL2 and IL-8 enhanced the capacity of BMMSC to support adhesion of ALL cells. CCL2 and IL-8 were also found to enhance BMMSC survival and to increase their proliferation. ALL cells were not directly affected by CCL2 or IL-8. Conclusions. The leukemic BM microenvironment had increased levels of CCL2 and IL-8. These chemokines are known to have suppressive effects in normal hematopoiesis. Our data indicate that CCL2 and IL-8 have a positive impact on BMMSC survival, proliferation, and adhesiveness to ALL cells. Leukemia-associated CCL2 and IL-8 upregulation may represent one possible mechanism of microenvironment perversion in favor of ALL cells. Pediatr Blood Cancer 2011;56:568-577. (C) 2010 Wiley-Liss, Inc. (AU) | |
| Processo FAPESP: | 06/01158-3 - Acao da ccl2 na sobrevivencia e proliferacao da leucemia linfoide aguda pediatrica, em sistema de co cultura com celulas do estroma da medula ossea. |
| Beneficiário: | Jaíra Ferreira de Vasconcellos |
| Linha de fomento: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 08/02106-2 - IGFBP7 e a quimioresistência da Leucemia Linfóide Aguda Pediátrica |
| Beneficiário: | Angelo Brunelli Albertoni Laranjeira |
| Linha de fomento: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 05/02390-4 - Ação da CCL2 e IL-8 na sobrevivência e proliferação da leucemia linfóide aguda pediátrica, em sistema de co-cultura com células do estroma da medula óssea |
| Beneficiário: | José Andrés Yunes |
| Linha de fomento: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 06/02083-7 - Caracterizacao funcional de proteinas envolvidas no controle da expressao genica. |
| Beneficiário: | Nilson Ivo Tonin Zanchin |
| Linha de fomento: | Auxílio à Pesquisa - Regular |