title: BMP-2 inhibits the tumorigenicity of cancer stem cells in human osteosarcoma OS99-1 cell line.
abstract: Previously, based on high ALDH activity, we showed that cancer stem cells (CSCs) could be identified as ALDH(br) cells from an aggressive human osteosarcoma OS99-1 cell line. In this study, we evaluate the impact of BMP-2 on CSCs.Three types of BMP receptors were expressed in freshly sorted ALDH(br) cells. In vitro, growth of the sorted ALDH(br) cells was inhibited by BMP-2. Using RT-PCR analysis, BMP-2 was found to down-regulate the expression of embryonic stem cell markers Oct3/4, Nanog, and Sox-2, and up-regulate the transcription of osteogenic markers Runx-2 and Collagen Type I. In vivo, all animals receiving ALDH(br) cells treated with BMP-2 did not form significant tumors, while untreated ALDH(br) cells developed large tumor masses in NOD/SCID mice. Immunostaining confirmed few Ki-67 positive cells were present in the sections of tumor containing ALDH(br) cells treated with BMP-2. These results suggest that BMP-2 suppresses tumor growth by reducing the gene expression of tumorigenic factors and inducing the differentiation of CSCs in osteosarcoma. BMP-2 or BMP-2-mimetic drugs, if properly delivered to tumor and combined with traditional therapies, may therefore provide a new therapeutic option for treatment of osteosarcoma.
authors.affiliation: Spine Research Laboratory, Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Paul
authors.initials: P
authors.lastname: Park
authors.forename: Huina
authors.initials: H
authors.lastname: Zhang
authors.forename: Frank
authors.initials: F
authors.lastname: La Marca
authors.forename: Amy
authors.initials: A
authors.lastname: Claeson
authors.forename: Juan
authors.initials: J
authors.lastname: Valdivia
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Lin
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D019394:Ki-67 Antigen / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055748:SOXB1 Transcription Factors / Q000235:genetics
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D018398:Homeodomain Proteins; D019394:Ki-67 Antigen; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C493709:RUNX2 protein, human; D055748:SOXB1 Transcription Factors; D000444:Aldehyde Dehydrogenase