TAS‐115 inhibits PDGFRα/AXL/FLT‐3 signaling and suppresses lung metastasis of osteosarcoma

Autor: Sho Nakai, Naohiro Yasuda, Satoshi Takenaka, Norifumi Naka, Takaaki Nakai, Yoshinori Imura, Shutaro Yamada, Hidetatsu Outani, Hideki Yoshikawa, Kenichiro Hamada
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Lung Neoplasms
Receptor
Platelet-Derived Growth Factor alpha
Lung metastasis
TAS‐115
Mice
0302 clinical medicine
Cell Movement
Medicine
Phosphorylation
lcsh:QH301-705.5
Research Articles
Mice
Inbred C3H
lung metastasis
Thiourea
Proto-Oncogene Proteins c-met
030220 oncology & carcinogenesis
Quinolines
Osteosarcoma
Female
Signal transduction
Signal Transduction
Research Article
musculoskeletal diseases
molecular targeted therapy
Alpha (ethology)
Bone Neoplasms
LM8
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Growth factor receptor
Cell Line
Tumor
Proto-Oncogene Proteins
osteosarcoma
Animals
Humans
Protein Kinase Inhibitors
Survival rate
neoplasms
Cell Proliferation
business.industry
Receptor Protein-Tyrosine Kinases
medicine.disease
Axl Receptor Tyrosine Kinase
030104 developmental biology
fms-Like Tyrosine Kinase 3
lcsh:Biology (General)
Cell culture
Cancer research
business
Proto-Oncogene Proteins c-akt
Zdroj: FEBS Open Bio, Vol 10, Iss 5, Pp 767-779 (2020)
FEBS Open Bio
ISSN: 2211-5463
Popis: Osteosarcoma is the most common malignant bone tumor in adolescence and childhood. Metastatic osteosarcoma has a poor prognosis with an overall 5‐year survival rate of approximately 20%. TAS‐115 is a novel multiple receptor tyrosine kinase inhibitor that is currently undergoing clinical trials. Using the mouse highly lung‐metastatic osteosarcoma cell line, LM8, we showed that TAS‐115 suppressed the growth of subcutaneous grafted tumor and lung metastasis of osteosarcoma at least partially through the inhibition of platelet‐derived growth factor receptor alpha, AXL, and Fms‐like tyrosine kinase 3 phosphorylation. We also show that these signaling pathways are activated in various human osteosarcoma cell lines and are involved in proliferation. Our results suggest that TAS‐115 may have potential for development into a novel treatment for metastatic osteosarcoma.
TAS‐115 suppressed the growth of subcutaneous grafted tumor and lung metastasis of a mouse spontaneous highly metastatic osteosarcoma (OS) cell line, LM8. TAS‐115 exerts antitumor effects against OS cell lines partially via the inhibition of PDGFRα, AXL, and FLT‐3 signaling. TAS‐115 may be a potential novel therapeutic agent for patients with metastatic OS.
Databáze: OpenAIRE
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