Fidelity of a PDX-CR model for bladder cancer

Abdul M. Mondal, Ai Hong Ma, Guangzhao Li, Ewa Krawczyk, Ruan Yuan, Jie Lu, Richard Schlegel, Lambros Stamatakis, Keith J. Kowalczyk, George K. Philips, Chong-Xian Pan, Xuefeng Liu

Research output: Contribution to journalArticle

Abstract

Patient-derived xenografts (PDXs) are widely recognised as a more physiologically relevant preclinical model than standard cell lines, but are expensive and low throughput, have low engraftment rate and take a long time to develop. Our newly developed conditional reprogramming (CR) technology addresses many PDX drawbacks, but lacks many in vivo factors. Here we determined whether PDXs and CRCs of the same cancer origin maintain the biological fidelity and complement each for translational research and drug development. Four CRC lines were generated from bladder cancer PDXs. Short tandem repeat (STR) analyses revealed that CRCs and their corresponding parental PDXs shared the same STRs, suggesting common cancer origins. CRCs and their corresponding parental PDXs contained the same genetic alterations. Importantly, CRCs retained the same drug sensitivity with the corresponding downstream signalling activity as their corresponding parental PDXs. This suggests that CRCs and PDXs can complement each other, and that CRCs can be used for in vitro fast, high throughput and low cost screening while PDXs can be used for in vivo validation and study of the in vivo factors during translational research and drug development.

Original languageEnglish (US)
JournalBiochemical and Biophysical Research Communications
DOIs
StatePublished - Jan 1 2019

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Heterografts
Urinary Bladder Neoplasms
Translational Medical Research
Throughput
Pharmaceutical Preparations
Validation Studies
Research
Microsatellite Repeats
Neoplasms
Screening
Cells
Technology
Costs and Cost Analysis
Cell Line

Keywords

  • Bladder cancer
  • Cell line models
  • Conditional reprogramming
  • Drug discovery
  • Patient derived xenograft

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fidelity of a PDX-CR model for bladder cancer. / Mondal, Abdul M.; Ma, Ai Hong; Li, Guangzhao; Krawczyk, Ewa; Yuan, Ruan; Lu, Jie; Schlegel, Richard; Stamatakis, Lambros; Kowalczyk, Keith J.; Philips, George K.; Pan, Chong-Xian; Liu, Xuefeng.

In: Biochemical and Biophysical Research Communications, 01.01.2019.

Research output: Contribution to journalArticle

Mondal, AM, Ma, AH, Li, G, Krawczyk, E, Yuan, R, Lu, J, Schlegel, R, Stamatakis, L, Kowalczyk, KJ, Philips, GK, Pan, C-X & Liu, X 2019, 'Fidelity of a PDX-CR model for bladder cancer', Biochemical and Biophysical Research Communications. https://doi.org/10.1016/j.bbrc.2019.06.165
Mondal, Abdul M. ; Ma, Ai Hong ; Li, Guangzhao ; Krawczyk, Ewa ; Yuan, Ruan ; Lu, Jie ; Schlegel, Richard ; Stamatakis, Lambros ; Kowalczyk, Keith J. ; Philips, George K. ; Pan, Chong-Xian ; Liu, Xuefeng. / Fidelity of a PDX-CR model for bladder cancer. In: Biochemical and Biophysical Research Communications. 2019.
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AU - Stamatakis, Lambros

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