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1.
Stem Cell Res Ther ; 9(1): 34, 2018 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-29433559

RESUMO

CXCR4 was the first receptor identified for CXCL12, but a second receptor, CXCR7, has also been described and its function in hematopoietic cells remains unknown. By inhibition of CXCR4 and/or CXCR7, we showed that CXCR7 participates in normal CD34+ and U937 cell migration and prevents downregulation of CXCR4 by CXCL12 stimulation. In addition, CXCR7 contributes to homing of acute myeloid leukemia and normal progenitor cells to the bone marrow and spleen of NOD/SCID mice. In summary, this study shows an essential role of CXCR7, together with CXCR4, in the control of normal and malignant hematopoietic cell migration and homing induced by CXCL12.


Assuntos
Movimento Celular , Quimiocina CXCL12/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Leucemia Mieloide Aguda/metabolismo , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/metabolismo , Receptores CXCR/metabolismo , Animais , Células-Tronco Hematopoéticas/patologia , Xenoenxertos , Humanos , Leucemia Mieloide Aguda/patologia , Camundongos , Camundongos Nus , Camundongos SCID , Transplante de Neoplasias , Células-Tronco Neoplásicas/patologia , Células U937
2.
PLoS One ; 9(1): e85926, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24497931

RESUMO

Recently, a novel CXCL12-binding receptor, has been identified. This CXCL12-binding receptor commonly known as CXCR7 (CXC chemokine receptor 7), has lately, based on a novel nomenclature, has received the name ACKR3 (atypical chemokine receptor 3). In this study, we aimed to investigate the expression of CXCR7 in leukemic cells, as well as its participation in CXCL12 response. Interesting, we clearly demonstrated that CXCR7 is highly expressed in acute lymphoid leukemic cells compared with myeloid or normal hematopoietic cells and that CXCR7 contributed to T-acute lymphoid leukemic cell migration induced by CXCL12. Moreover, we showed that the cellular location of CXCR7 varied among T-lymphoid cells and this finding may be related to their migration capacity. Finally, we hypothesized that CXCR7 potentiates CXCR4 response and may contribute to the maintenance of leukemia by initiating cell recruitment to bone marrow niches that were once occupied by normal hematopoietic stem cells.


Assuntos
Quimiocina CXCL12/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Receptores CXCR4/metabolismo , Receptores CXCR/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzilaminas , Western Blotting , Medula Óssea/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Ciclamos , Feminino , Citometria de Fluxo , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Humanos , Células Jurkat , Células K562 , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Interferência de RNA , Receptores CXCR/sangue , Receptores CXCR/genética , Receptores CXCR4/antagonistas & inibidores , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células U937 , Adulto Jovem
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