BMP7 as an inhibitor of melanoma metastatis
Kofi
anti-fibrotic effects via BMP7 in other cells.
Cancer Sci. 2009 Nov;100(11):2218-25. Epub 2009 Jul 30.
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Bone morphogenetic protein 7 induces mesenchymal-to-epithelial
transition in melanoma cells, leading to inhibition of metastasis.
Na YR, Seok SH, Kim DJ, Han JH, Kim TH, Jung H, Lee BH, Park JH.
Department of Laboratory Animal Medicine, College of Veterinary Medicine
and KRF Zoonotic Disease Priority Research Institute, Seoul National
University, Seoul, Korea.
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.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19735263