MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors.
Gene Ther
; 18(7): 692-701, 2011 Jul.
Article
en En
| MEDLINE
| ID: mdl-21368903
ABSTRACT
Matrix metalloproteinases (MMPs) are a family of proteinases known to have a role in cell migration. In the present study, we evaluated the role of MMP-2 on tropism of human umbilical cord blood-derived stem cells (hUCBSCs) in a human medulloblastoma tumor model. Consequences of MMP-2 inhibition on stem cell tropism towards medulloblastoma were studied in terms of stem cell migration by using cell culture inserts, transwell chamber assay, western blotting for MMP-2 and migratory molecules, and immunohistochemistry. Conditioned medium from Daoy/D283 cells infected with adenoviral vector encoding MMP-2 small interfering RNA (siRNA) (Ad-MMP-2 si)-reduced stem cell migration as compared with conditioned medium from mock and scrambled vector (Ad-SV) infected cells. In addition, MMP-2 inhibition in the tumor cells decreased the expression of stromal cell-derived factor 1 (SDF1) in the tumor-conditioned medium, which results in impaired SDF1/CXCR4 signaling leading to decreased stem cell tropism towards the tumor cells. We further show that MMP-2 inhibition in the tumor cells repressed stem cell tropism towards medulloblastoma tumors in vivo. In summary, we conclude that hUCBSCs can integrate into human medulloblastoma after local delivery and that MMP-2 expression by the tumor cells mediates this response through the SDF1/CXCR4 axis.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Movimiento Celular
/
Técnicas de Transferencia de Gen
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Metaloproteinasa 2 de la Matriz
/
Células Madre Mesenquimatosas
/
Meduloblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos