Inhibition of the activin receptor signaling pathway: A novel intervention against osteosarcoma

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DOI

  • Daniela Meier, Balgrist University Hospital
  • ,
  • Andreas Lodberg
  • Ana Gvozdenovic, Balgrist University Hospital
  • ,
  • Giovanni Pellegrini, University of Zurich
  • ,
  • Olga Neklyudova, Balgrist University Hospital
  • ,
  • Walter Born, Balgrist University Hospital
  • ,
  • Bruno Fuchs, Balgrist University Hospital
  • ,
  • Marco Eijken
  • Sander M Botter, Balgrist University Hospital

Osteosarcoma is a cancer of pathological bone remodeling with high mortality and severe comorbidity. New therapies are urgently needed. Activin A, a member of the transforming growth factor β (TGFβ) superfamily, has been suggested to stimulate proliferation and invasion of osteosarcoma cells in vitro, thus representing a potential therapeutic target. In this study, inhibition of the activin receptor signaling pathway was explored as a therapy for osteosarcoma. In a murine intratibial osteosarcoma xenograft model, two types of inhibitors were tested: (a) a soluble activin type IIA decoy receptor (ActRIIA-mFc), or (b) a modified variant of follistatin (FSTΔHBS -hFc), either alone or in combination with a bisphosphonate. Both inhibitors reduced primary tumor development by nearly 50% compared to vehicle treatment. When ActRIIA-mFc was combined with bisphosphonate, the effect on tumor size became even more pronounced (78% reduction vs. vehicle). Moreover, FSTΔHBS -hFc increased body weight in the face of tumor progression (14% increase vs. vehicle), and ActRIIA-mFc reduced the number of lung metastases when combined with bisphosphonate. The present study demonstrates a novel approach to treating osteosarcoma and encourages further investigation of inhibition of the activin receptor signaling pathway as an intervention against the disease.

Original languageEnglish
JournalCancer Medicine
Volume10
Issue1
Number of pages11
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

    Research areas

  • activin type II receptor, follistatin, osteosarcoma, pathological bone remodeling, zoledronic acid, ZOLEDRONIC ACID, CANCER CACHEXIA, LUNG METASTASIS, BISPHOSPHONATES, SURVIVAL, FOLLISTATIN, PROLONGS, BINDING

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