title: BMP-2 inhibits tumor growth of human renal cell carcinoma and induces bone formation.
abstract: Bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor superfamily, has been shown to have inhibitory effect on many tumor types. However, the effect of BMP-2 on human renal cell carcinoma (RCC) is still unknown. We previously showed that BMP-2 inhibits tumorigenicity of cancer stem cells in human osteosarcoma OS99-1 cells. Our study investigates the effect of BMP-2 on human RCC using ACHN and Caki-2 cell lines. Three types of BMP receptors were found to be expressed in ACHN and Caki-2 cells. In vitro, BMP-2 was found to inhibit the growth of ACHN and Caki-2 cells. The antiproliferative effect seems to be due to cell cycle arrest in the G1 phase, which was revealed by flow cytometry analysis. Using reverse transcriptase polymerase chain reaction analysis, we demonstrated BMP-2 upregulated osteogenic markers Runx-2 and Collagen Type I gene expression in ACHN and Caki-2 cells. Treatment of ACHN and Caki-2 cells with BMP-2 induced a rapid phosphorylation of Smad1/5/8. In vivo, all animals receiving low number of ACHN (1 × 10(4)) and Caki-2 (5 × 10(4)) cells treated with 30 μg of BMP-2 per animal showed limited tumor growth with significant bone formation, whereas untreated cells developed large tumor masses without bone formation in immunodeficient non-obese diabetic (NOD)/severe combined immunodeficient (SCID) mice. These results suggest that BMP-2 inhibits growth of RCC as well as causes induction of osseous bone formation. Further research is needed to determine the relationship between inhibition of cell proliferation and bone induction.
authors.affiliation: Spine Research Laboratory, Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, 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: Khoi
authors.initials: K
authors.lastname: Than
authors.forename: Shayan
authors.initials: S
authors.lastname: Rahman
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Lin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002453:Cell Cycle; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010012:Osteogenesis; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D055396:Bone Morphogenetic Protein 2; D012333:RNA, Messenger