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

Lin Wang, Paul Park, Frank La Marca, Khoi D. Than, Chia Ying Lin

Research output: Contribution to journalArticle

24 Scopus citations

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 ALDHbr cells. The ALDHbr 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 (ALDHlo cells), generating new tumors with as few as 25 cells in mice.Results: In vitro, BMP-2 was found to inhibit the ALDHbr 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 ALDHbr cells (5 × 103) 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.

Original languageEnglish (US)
Pages (from-to)1013-1024
Number of pages12
JournalJournal of Cancer Research and Clinical Oncology
Volume141
Issue number6
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Keywords

  • Aldehyde dehydrogenase
  • BMP-2
  • Cancer stem cells
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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