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

被引：4

作者：

Yasuda, Naohiro ^{[1
]}

Takenaka, Satoshi ^{[1
]}

Nakai, Sho ^{[1
]}

Nakai, Takaaki ^{[2
]}

Yamada, Shutaro ^{[3
]}

Imura, Yoshinori ^{[4
]}

Outani, Hidetatsu ^{[1
]}

Hamada, Kenichiro ^{[1
]}

Yoshikawa, Hideki ^{[1
,5
]}

Naka, Norifumi ^{[1
,4
]}

机构：

[1] Osaka Univ, Dept Orthopaed Surg, Grad Sch Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan

[2] Kawachi Gen Hosp, Dept Orthopaed Surg, Higashiosaka, Osaka, Japan

[3] Yao Municipal Hosp, Dept Orthopaed Surg, Yao, Japan

[4] Osaka Int Canc Inst, Musculoskeletal Oncol Serv, Osaka, Japan

[5] Toyonaka City Hosp, Dept Orthopaed Surg, Toyonaka, Osaka, Japan

来源：

FEBS OPEN BIO | 2020年 / 10卷 / 05期

关键词：

LM8; lung metastasis; molecular targeted therapy; osteosarcoma; TAS-115; TYROSINE KINASE INHIBITOR; FACTOR-KAPPA-B; NEOADJUVANT CHEMOTHERAPY; TUMOR PROGRESSION; PHASE-II; MET; ACTIVATION; IMATINIB; SARCOMA;

D O I：

10.1002/2211-5463.12827

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：767 / 779

页数：13

共 21 条

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