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• W2768536618 abstract "// Zhiwei Qiao 1 , Kumiko Shiozawa 1 and Tadashi Kondo 1 1 Division of Rare Cancer Research, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan Correspondence to: Tadashi Kondo, email: takondo@ncc.go.jp Keywords: pazopanib; resistance; synovial sarcoma; tyrosine kinase Received: August 08, 2017     Accepted: October 28, 2017     Published: November 28, 2017 ABSTRACT Pazopanib, a multitarget tyrosine kinase (TK) inhibitor, has been approved for treatment of soft tissue sarcoma. Elucidation of the molecular background of pazopanib resistance should lead to improved clinical outcomes in sarcomas; accordingly, we investigated this in synovial sarcoma using a proteomic approach. Pazopanib sensitivity was examined in four synovial sarcoma cell lines: SYO-1, HS-SYII, 1273/99, and YaFuSS. The 1273/99 cell line showed significantly higher IC 50 values than the others for pazopanib. Expression levels of 90 TKs in the cell lines were examined by western blotting. Among these, the levels of PDGFRB, DDR1, AXL, MET, and PYK2 were higher, and those of FGFR1 and VEGFR3 were lower in the 1273/99 cell line than the other cell lines. Gene silencing analysis of the TKs upregulated in 1273/99 cells showed differing effects on cell growth: PDGFRB , MET, and PYK2 knockdown induced cell growth inhibition, whereas DDR1 and AXL knockdown did not influence cell growth. Using the PamChip peptide microarray, we found that 18 peptide substrates were highly phosphorylated in the 1273/99 cell line compared with other cell lines. Using the PhosphoNet database, we found that kinases FGFR3, RET, VEGFR1, EPHA2, EPHA4, TRKA, and SRC phosphorylated these 18 peptide substrates. Moreover, the results for overexpressed and aberrantly activated TKs in pazopanib-resistant cells showed no overlap. Taken together, our study indicates that identification of comprehensive TK profiles represents an essential approach to determining the molecular background of pazopanib resistance in synovial sarcoma." @default.
• W2768536618 created "2017-12-04" @default.
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• W2768536618 date "2017-11-28" @default.
• W2768536618 modified "2023-10-17" @default.
• W2768536618 title "Proteomic approach toward determining the molecular background of pazopanib resistance in synovial sarcoma" @default.
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• W2768536618 doi "https://doi.org/10.18632/oncotarget.22730" @default.
• W2768536618 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5752544" @default.
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