BMP-2 inhibits tumor-initiating ability in human renal cancer stem cells and induces bone formation.
J Cancer Res Clin Oncol
; 141(6): 1013-24, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25431339
ABSTRACT
PURPOSE:
We have previously shown that BMP-2 induces bone formation and inhibits tumorigenicity of cancer stem cells (CSCs) in a human osteosarcoma OS99-1 cell line. In this study, we sought to determine whether BMP-2 can similarly induce bone formation and inhibit the tumorigenicity of renal CSCs identified based on aldehyde dehydrogenase (ALDH) activity in renal cell carcinoma (RCC) cell lines and primary tumors.METHODS:
Using a xenograft model in which cells from human RCC cell lines ACHN, Caki-2, and primary tumors were grown in NOD/SCID mice, renal CSCs were identified as a subset of ALDH(br) cells. The ALDH(br) cells possessed a greater colony-forming efficiency, higher proliferative output, increased expression of stem cell marker genes Oct3/4A, Nanog, renal embryonic marker Pax-2, and greater tumorigenicity compared to cells with low ALDH activity (ALDH(lo) cells), generating new tumors with as few as 25 cells in mice.RESULTS:
In vitro, BMP-2 was found to inhibit the ALDH(br) cell growth, down-regulate the expression of embryonic stem cell markers, and up-regulate the transcription of osteogenic markers. In vivo, all animals receiving a low number of ALDH(br) cells (5 × 10(3)) from ACHN, Caki-2, and primary tumor xenografts treated with 30 µg BMP-2 per animal showed limited tumor growth with significant bone formation, while untreated cells developed large tumor masses without bone formation.CONCLUSIONS:
These results suggest that BMP-2 inhibits the tumor-initiating ability of renal CSCs and induces osseous bone formation. BMP-2 may therefore provide a beneficial strategy for human RCC treatment by targeting the CSC-enriched population.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteogênese
/
Células-Tronco Neoplásicas
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Neoplasias Ósseas
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Carcinoma de Células Renais
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Osteossarcoma
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Transformação Celular Neoplásica
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Aldeído Desidrogenase
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Proteína Morfogenética Óssea 2
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Neoplasias Renais
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Cancer Res Clin Oncol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos