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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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.

OriginalsprogEngelsk
TidsskriftCancer Medicine
Vol/bind10
Nummer1
Antal sider11
DOI
StatusUdgivet - jan. 2021

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