| Full text | |
| Author(s): |
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]
Total Authors: 8
|
| Affiliation: | [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
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | PEDIATRIC BLOOD & CANCER; v. 56, n. 4, p. 568-577, APR 2011. |
| Web of Science Citations: | 24 |
| Abstract | |
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) | |
| FAPESP's process: | 05/02390-4 - Role of CCL2 and IL-8 on the survival and proliferation of childhood B-lineage acute lymphoblastic leukemia cells co-cultured with bone marrow stromal cells |
| Grantee: | José Andrés Yunes |
| Support type: | Regular Research Grants |
| FAPESP's process: | 08/02106-2 - IGFBP7 role in chemotherapy resistance of Pediatric Acute Lymphoblastic Leukemia |
| Grantee: | Angelo Brunelli Albertoni Laranjeira |
| Support type: | Scholarships in Brazil - Doctorate |