Proteomic approach toward determining the molecular background of pazopanib resistance in synovial sarcoma

Oncotarget
Zhiwei QiaoTadashi Kondo

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 IC50 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, an...Continue Reading

References

Mar 3, 1998·Biochemical and Biophysical Research Communications·M P LutzG Adler
Jul 9, 2004·Pathology, Research and Practice·Hermann Lage
Apr 9, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Tatsuya IshibeJunya Toguchida
Sep 15, 2007·Cancer Treatment Reviews·Jian-Ting Zhang, Yang Liu
Oct 13, 2007·Nature Reviews. Drug Discovery·Robyn P AraujoEmanuel F Petricoin
Aug 13, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Roberto BiancoGiampaolo Tortora
Jul 2, 2009·Cancer Research·Arend H SikkemaEveline S J M de Bont
Feb 24, 2010·Cancer Letters·Victoria C HodgkinsonLynn Cawkwell
May 18, 2010·Expert Review of Anticancer Therapy·Ronald M Bukowski
Dec 8, 2010·Leukemia & Lymphoma·Arja Ter ElstEveline S J M de Bont
Oct 4, 2011·Journal of Proteomics·Xin-Hui LiZhi-Qiang Xiao
Jul 7, 2012·Journal of Pain & Palliative Care Pharmacotherapy·UNKNOWN Food And Drug Administration, Public Health Service, U.S. Department Of Health And Human Services
Feb 13, 2014·Proteomics·Corinne Solier, Hanno Langen
Sep 3, 2014·The Pharmacogenomics Journal·Y ZhengY Tong
Jun 16, 2015·Scientific Reports·Benjamin D FergusonRavi Salgia
Nov 1, 2015·Journal of Alzheimer's Disease : JAD·Andrea F N RosenbergerSaskia M van der Vies

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Citations

May 28, 2019·Signal Transduction and Targeted Therapy·Alex T J LeePaul H Huang
May 18, 2020·Signal Transduction and Targeted Therapy·Alex T J LeePaul H Huang
Apr 25, 2021·Pediatric Blood & Cancer·Marissa A JustLars M Wagner
Dec 4, 2021·Journal of Experimental & Clinical Cancer Research : CR·Cinzia LanziGiuliana Cassinelli

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Methods Mentioned

BETA
transfection
electrophoresis

Software Mentioned

PamGene
PamChip
ImageJ
Bioconductor limma

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