Bone morphogenetic protein 7 induces mesenchymal-to-epithelial transition in melanoma cells, leading to inhibition of metastasis.
Bone morphogenetic protein (BMP) 7 counteracts physiological epithelial-to-mesenchymal transition, a process that is indicative of epithelial plasticity in developmental stages. Because epithelial-to-mesenchymal transition and its reversed process mesenchymal-to-epithelial transition (MET) are also involved in cancer progression, we investigated whether BMP7 plays a role in WM-266-4 melanoma cell growth and metastasis. An MTT assay was conducted in WM-266-4 and HEK293T cell lines to show the cell growth inhibition ability of BMP7 and cisplatin. Semiquantitative RT-PCR was used to determine MET in morphologically changed BMP7-treated melanoma cells. MET-induced cells expressed less a basic helix-loop-helix transcription factor (TWIST) in western blot analysis, and we confirm that BMP receptor (Alk2) siRNA transduction could restore TWIST protein expression via blocking of Smad 1, 5 and 8 signaling. Matrigel invasion and cell migration assays were done to investigate the BMP7-induced metastasis inhibition ability. BMP7 treatment only slightly reduced cell growth rate, but induced apparent MET. BMP7 also reduced the invasion and migration ability. Furthermore, BMP7 reduced the resistance of WM-266-4 cells to cisplatin. Collectively, our findings indicate that the metastatis inhibition ability of BMP7 is involved in MET, and that BMP7 could be used as a potential metastasis inhibitor in human melanoma cells.
Na
Yi-Rang
YR
Department of Laboratory Animal Medicine, College of Veterinary Medicine and KRF Zoonotic Disease Priority Research Institute, Seoul National University, Seoul, Korea.
Seok
Seung-Hyeok
SH
Kim
Dong-Jae
DJ
Han
Ju-Hee
JH
Kim
Tae-Hyoun
TH
Jung
Hyun
H
Lee
Byoung-Hee
BH
Park
Jae-Hak
JH
D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D052004:Bone Morphogenetic Protein Receptors / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004847:Epithelial Cells / Q000473:pathology*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology* / Q000556:secondary*; D008648:Mesoderm / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors / Q000502:physiology
D055419:Bone Morphogenetic Protein 7; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D052004:Bone Morphogenetic Protein Receptors; D002945:Cisplatin