Bone morphogenetic protein-9 induces epithelial to mesenchymal transition in hepatocellular carcinoma cells
Epithelial-mesenchymal transition (EMT) is an important mechanism to initiate cancer invasion and metastasis. Bone morphogenetic protein (BMP)-9 is a member of the transforming growth factor (TGF)-β superfamily. It has been suggested to play a role in cancer development in some non-hepatic tumors. I...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
February 13, 2013
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| In: |
Cancer science
Year: 2013, Jahrgang: 104, Heft: 3, Pages: 398-408 |
| ISSN: | 1349-7006 |
| DOI: | 10.1111/cas.12093 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1111/cas.12093 Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/cas.12093 
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| Verfasserangaben: | Qi Li, Xing Gu, Honglei Weng, Shahrouz Ghafoory, Yan Liu, Teng Feng, Johanna Dzieran, Li Li, Iryna Ilkavets, Marianna Kruithof- de Julio, Stefan Munker, Alexander Marx, Albrecht Piiper, Eduardo Augusto Alonso, Norbert Gretz, Chunfang Gao, Stefan Wölfl, Steven Dooley and Katja Breitkopf-Heinlein |
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| 520 | |a Epithelial-mesenchymal transition (EMT) is an important mechanism to initiate cancer invasion and metastasis. Bone morphogenetic protein (BMP)-9 is a member of the transforming growth factor (TGF)-β superfamily. It has been suggested to play a role in cancer development in some non-hepatic tumors. In the present study, two hepatocellular carcinoma (HCC) lines, HLE and HepG2, were treated with BMP-9 in vitro, and phenotypic changes and cell motility were analyzed. In situ hybridization (ISH) and immunohistochemical analyses were performed with human HCC tissue samples in order to assess expression levels of BMP-9. In vivo, BMP-9 protein and mRNA were expressed in all the tested patients to diverse degrees. At the protein level, mildly positive (1 + ) BMP-9 staining could be observed in 25/41 (61%), and moderately to strongly positive (2 + ) in 16/41 (39%) of the patients. In 27/41 (65%) patients, the BMP-9 protein expression level was consistent with the mRNA expression level as measured by ISH. In those patients with 2 + protein level, nuclear pSmad1 expression in cancer cells was also significantly increased. Expression of BMP-9 was positively related to nuclear Snail expression and reversely correlated to cell surface E-cadherin expression, although this did not reach statistical significance. Expression levels of BMP-9 were significantly associated with the T stages of the investigated tumors and high levels of BMP-9 were detected by immunofluorescence especially at the tumor borders in samples from an HCC mouse model. In vitro, BMP-9 treatment caused a reduction of E-cadherin and ZO-1 and an induction of Vimentin and Snail expression. Furthermore, cell migration was enhanced by BMP-9 in both HCC cell lines. These results imply that EMT induced by BMP-9 is related to invasiveness of HCC. | ||
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