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

doi:10.1016/j.bbrc.2019.06.165

Fidelity of a PDX-CR model for bladder cancer

Biochem Biophys Res Commun. 2019 Sep 10;517(1):49-56. doi: 10.1016/j.bbrc.2019.06.165. Epub 2019 Jul 11.

Authors

Affiliations

¹ Center for Cell Reprograming, Department of Pathology, Georgetown University Medical Center, Washington DC, USA.
² Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Washington DC, USA.
³ Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Washington DC, USA; Department of Urology, Renmin Hospital, Wuhan University, Washington DC, USA.
⁴ Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA; Department of Urology, MedStar Washington Hospital Center, Washington DC, USA.
⁵ Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA; Department of Urology, MedStar Georgetown Hospital, Washington DC, USA.
⁶ Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA; Department of Oncology, MedStar Georgetown Hospital, Washington DC, USA.
⁷ Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Washington DC, USA; VA Northern California Health Care System, Mather, CA, USA. Electronic address: [email protected].
⁸ Center for Cell Reprograming, Department of Pathology, Georgetown University Medical Center, Washington DC, USA; Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA. Electronic address: [email protected].

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.

Keywords: Bladder cancer; Cell line models; Conditional reprogramming; Drug discovery; Patient derived xenograft.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Cell Culture Techniques / economics
Cell Culture Techniques / methods
Disease Models, Animal
Drug Development
Drug Resistance, Neoplasm
Humans
Mice
Mutation
Translational Research, Biomedical
Tumor Cells, Cultured
Urinary Bladder Neoplasms / drug therapy*
Urinary Bladder Neoplasms / genetics
Urinary Bladder Neoplasms / pathology
Xenograft Model Antitumor Assays / economics
Xenograft Model Antitumor Assays / methods*

Substances

Antineoplastic Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding