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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Increased CCL2 and IL-8 in the Bone Marrow Microenvironment in Acute Lymphoblastic Leukemia

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Autor(es):
de Vasconcellos, Jaira Ferreira [1, 2] ; Albertoni Laranjeira, Angelo Brunelli [1] ; Tonin Zanchin, Nilson Ivo [3] ; Otubo, Rosemary [1] ; Vaz, Thais Haline [3] ; Cardoso, Angelo Almeida [4] ; Brandalise, Silvia Regina [1, 5] ; Yunes, Jose Andres [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Ctr Infantil Boldrini, Lab Biol Mol, BR-13083210 Campinas, SP - Brazil
[2] Univ Estadual Campinas, Fac Med Sci, Dept Med Genet, 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: 06/02083-7 - Caracterizacao funcional de proteinas envolvidas no controle da expressao genica.
Beneficiário:Nilson Ivo Tonin Zanchin
Linha de fomento: Auxílio à Pesquisa - Regular
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: 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: 08/02106-2 - IGFBP7 e a quimioresistência da Leucemia Linfóide Aguda Pediátrica
Beneficiário:Angelo Brunelli Albertoni Laranjeira
Linha de fomento: Bolsas no Brasil - Doutorado