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- Title
BMP-2 inhibits tumor-initiating ability in human renal cancer stem cells and induces bone formation.
- Authors
Wang, Lin; Park, Paul; La Marca, Frank; Than, Khoi; Lin, Chia-Ying
- 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 cells. The ALDH 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 cells), generating new tumors with as few as 25 cells in mice. Results: In vitro, BMP-2 was found to inhibit the ALDH 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 cells (5 × 10) 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.
- Subjects
BONE morphogenetic proteins; CANCER stem cells; RENAL cancer; BONE growth; OSTEOSARCOMA; ALDEHYDE dehydrogenase
- Publication
Journal of Cancer Research & Clinical Oncology, 2015, Vol 141, Issue 6, p1013
- ISSN
0171-5216
- Publication type
Article
- DOI
10.1007/s00432-014-1883-0