Targeting Ligand Dependent BMP Signaling in Melanoma

Abstract

The studies in this project seek to understand the role of bone morphogenetic protein (BMP)signaling in melanoma and develop a treatment to target ligand-dependent BMP signaling. From previous studies we know that BMP signaling represses MITF expression and upregulates expression of neural crest genes, imparting a less-differentiated neural crest-like identity to melanoma cells. Inhibition of BMP signaling causes melanoma cells to express differentiation genes and die, preventing outgrowth of xenografted tumors. To target BMP signaling, we have created monoclonal antibodies that neutralize the BMP ligand GDF6. TheGDF6 gene is copy number amplified in melanoma cells, and elevated expression of GDF6 is associated with a dependence of melanoma cells on BMP activity. Preliminary results suggestanti-GDF6 monoclonal antibodies effectively inhibit BMP signaling, blocking growth and causing death of melanoma cells.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2021
Accession Number
AD1145737

Entities

People

  • Craig J Ceol

Organizations

  • University of Massachusetts Medical School

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DTIC Thesaurus Topics

  • Antibodies
  • Biological Staining And Labeling
  • Biomedical Research
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Covid-19
  • Culture Techniques
  • Cultured Cells
  • Embryos
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Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular and Cellular Biology
  • Oncology (Cancer Research).