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

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 interrelationships between prostatic cell types and the role of such interrelationships in organ development, disease progression, and response to drug treatments.

Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness between African Americans and European Americans

“…Therefore, the race-specific associations of genetic variations in SLCO2A1 and SLCO5A1 are aligned with both transporters being the predominant SLCO transporters expressed in prostate cancer tissue, and their cell type-specific expression in prostate cancer endothelial cells and epithelial cells. The cell type-specific expression of SLCO2A1 and SLCO5A1 in prostate tissue is supported by our recent report of RNA sequencing data generated from prostate epithelial cells and endothelial cells isolated from fresh clinical specimens of prostate tissue (38). However, knowledge on the biological functions and substrates of SLCO2A1 and SLCO5A1 in human prostate tissue is scant.…”

Comparison of tumor angiogenesis in subcutaneous and orthotopic LNCaP mouse models using contrast-enhanced ultrasound imaging

“…On immunofluorescence, there were significantly more blood vessels in orthotopic prostate tumors compared to subcutaneous tumors. These data indicate that the microenvironment at the orthotopic site and cellular-environmental interaction facilitated tumorigenesis of LNCaP cells ( 29 ).…”