Recapitulation of prostate tissue cell type-specific transcriptomes by an in vivo primary prostate tissue xenograft model.

Nelson T Gross,Yue Wu,Alejandro S Godoy,Jianmin Wang,Eduardo Cortes Gomez,Anica Watts,Michael V Fiandalo,Gary J Smith,Francisco J Esteban

doi:10.1371/journal.pone.0233899

Nelson T Gross, Yue Wu + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0233899

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Abstract

Studies of the normal functions and diseases of the prostate request in vivo models that maintain the tissue architecture and the multiple-cell type compartments of human origin in order to recapitulate reliably the interactions of different cell types. Cell type-specific transcriptomes are critical to reveal the roles of each cell type in the functions and diseases of the prostate. A primary prostate tissue xenograft model was developed using fresh human prostate tissue specimens transplanted onto male mice that were castrated surgically and implanted with a device to maintain circulating testosterone levels comparable to adult human males. Endothelial cells and epithelial cells were isolated from 7 fresh human prostate tissue specimens and from primary tissue xenografts established from 9 fresh human prostate tissue specimens, using antibody-conjugated magnetic beads specific to human CD31 and human EpCAM, respectively. Transcriptomes of endothelial, epithelial and stromal cell fractions were obtained using RNA-Seq. Global and function-specific gene expression profiles were compared in inter-cell type and inter-tissue type manners. Gene expression profiles in the individual cell types isolated from xenografts were similar to those of cells isolated from fresh tissue, demonstrating the value of the primary tissue xenograft model for studies of the inter-relationships between prostatic cell types and the role of such inter-relationships in organ development, disease progression, and response to drug treatments.

Highlights

Organogenesis and post-pubertal development of the prostate, as well as maintenance of tissue architecture and function in the adult prostate, are highly coordinated processes that involve interactions of multiple cell-type compartments, including endothelial, stromal and epithelial cells, that are tightly regulated by androgen [1, 2]
All experimental procedures were approved by the Roswell Park Comprehensive Cancer Center (RPCCC) Institutional Animal Care and Use Committee (IACUC) and were performed by trained staff of the RPCCC Mouse Tumor Model Resource (MTMR) core facility under IACUC protocol 1044M
The cell-type enriched samples (3 cell types) were prepared from 7 individual fresh prostate tissue specimens procured from 7 patients, and from 11 sets of tissue xenografts established from 11 patients: the patient set from which the xenografts were established did not overlap with the patient set from which fresh tissue was procured

Summary

Introduction

Organogenesis and post-pubertal development of the prostate, as well as maintenance of tissue architecture and function in the adult prostate, are highly coordinated processes that involve interactions of multiple cell-type compartments, including endothelial, stromal and epithelial cells, that are tightly regulated by androgen [1, 2]. An endothelial specific gene must be significantly differentially expressed in endothelial cells when compared to both other cell-types (epithelial or stromal) from both cell sources (fresh tissue or primary xenograft).

Results

Conclusion