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

Autor: Daniela Meier, Giovanni Pellegrini, Ana Gvozdenovic, Olga Neklyudova, Sander M. Botter, Marco Eijken, Bruno Fuchs, Walter Born, Andreas Lodberg
Přispěvatelé: University of Zurich
Rok vydání: 2020
Předmět:
0301 basic medicine
Cancer Research
Follistatin
pathological bone remodeling
Activin Receptors
Type II
Mice
SCID
zoledronic acid
0302 clinical medicine
BISPHOSPHONATES
BINDING
Antineoplastic Combined Chemotherapy Protocols
follistatin
1306 Cancer Research
CANCER CACHEXIA
10266 Clinic for Reconstructive Surgery
Receptor
Original Research
Cancer Biology
biology
Bone Density Conservation Agents
Diphosphonates
Primary tumor
Tumor Burden
Oncology
030220 oncology & carcinogenesis
SURVIVAL
Osteosarcoma
10046 Balgrist University Hospital
Swiss Spinal Cord Injury Center
2730 Oncology
Bone Remodeling
medicine.drug
Signal Transduction
PROLONGS
Recombinant Fusion Proteins
10184 Institute of Veterinary Pathology
Antineoplastic Agents
Bone Neoplasms
03 medical and health sciences
Necrosis
Cell Line
Tumor
osteosarcoma
medicine
2741 Radiology
Nuclear Medicine and Imaging
Animals
Humans
Radiology
Nuclear Medicine and imaging
activin type II receptor
Activin receptor signaling pathway
Tibia
medicine.disease
Xenograft Model Antitumor Assays
Immunoglobulin Fc Fragments
030104 developmental biology
Zoledronic acid
Tumor progression
Immunoglobulin G
LUNG METASTASIS
Cancer research
biology.protein
570 Life sciences
Transforming growth factor
Zdroj: Cancer Medicine
Meier, D, Lodberg, A, Gvozdenovic, A, Pellegrini, G, Neklyudova, O, Born, W, Fuchs, B, Eijken, M & M Botter, S 2021, ' Inhibition of the activin receptor signaling pathway : A novel intervention against osteosarcoma ', Cancer Medicine, vol. 10, no. 1 . https://doi.org/10.1002/cam4.3581
ISSN: 2045-7634
Popis: 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.
Inhibition of the activin receptor signaling pathway reduces tumor volume, pathological bone remodeling, and counteracts the cachexia that follows in the wake of osteosarcoma.
Databáze: OpenAIRE
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