Back
Full-text
Journal article

Embryonic bone morphogenetic protein and nodal induce invasion in melanocytes and melanoma cells.

  • Sinnberg T Section of Dermato-Oncology, Department of Dermatology, Tuebingen University Hospital, Liebermeisterstrasse 25, 72076 Tuebingen, Germany.
  • Niessner H Section of Dermato-Oncology, Department of Dermatology, Tuebingen University Hospital, Liebermeisterstrasse 25, 72076 Tuebingen, Germany.
  • Levesque MP Department of Dermatology, UniversitaetsSpital Zuerich, Gloriastrasse 31, 8091 Zuerich, Switzerland.
  • Dettweiler C Section of Dermato-Oncology, Department of Dermatology, Tuebingen University Hospital, Liebermeisterstrasse 25, 72076 Tuebingen, Germany.
  • Garbe C Section of Dermato-Oncology, Department of Dermatology, Tuebingen University Hospital, Liebermeisterstrasse 25, 72076 Tuebingen, Germany.
  • Busch C Section of Dermato-Oncology, Department of Dermatology, Tuebingen University Hospital, Liebermeisterstrasse 25, 72076 Tuebingen, Germany Christian.Busch@med.uni-tuebingen.de.
Show more…
  • 2018-05-03
Published in:
  • Biology open. - 2018
BMP
Epithelial-mesenchymal transition
Melanocytes
Melanoma
Nodal
English Despite recent progress in melanoma therapy via inhibition of activated oncogenes or immune stimulation, most stage IV melanoma patients still have limited survival times. Existing therapeutic approaches eventually fail to prevent further invasion and metastasis, which is driven by a morphological process termed epithelial-mesenchymal transition (EMT). We previously demonstrated that inhibition of EMT in melanoma cells via antagonizing the bone morphogenetic protein (BMP)-pathway abrogated EMT and neural crest migration of melanoma cells in chick embryos. Here, we show that BMP-2 is highly expressed in invasive melanoma cells and is elevated in the serum of stage IV melanoma patients compared to stage IB-IIC patients and healthy controls. Highly BMP-2-expressing melanoma cells display enhanced invasion in the rhombencephalon of the chick embryo. In addition to driving neural crest migration in the zebrafish embryo, the agonists BMP-2, BMP-7 and nodal induce EMT/invasion in radial growth phase melanoma cells and in human melanocytes in skin reconstructs. Blocking either BMP or nodal signaling by antagonists (noggin, lefty), or the Alk4/5/7-receptor inhibitor SB431542, decreases EMT and invasion of melanoma cells in human epidermal skin reconstructs. Together, our data suggest that inhibition of EMT-inducing pathways in melanoma might be a therapeutic approach to attenuate melanoma cell invasiveness.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/297333
Statistics
Document views: 20 File downloads:
  • Full-text: 0