BMP-2 inhibits tumor-initiating ability in human renal cancer stem cells and induces bone formation.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Wang, L; Park, P; La Marca, F; Than, KD; Lin, C-Y

Published Date

  • June 2015

Published In

Volume / Issue

  • 141 / 6

Start / End Page

  • 1013 - 1024

PubMed ID

  • 25431339

Pubmed Central ID

  • 25431339

Electronic International Standard Serial Number (EISSN)

  • 1432-1335

Digital Object Identifier (DOI)

  • 10.1007/s00432-014-1883-0

Language

  • eng

Conference Location

  • Germany