title: Differences in phenotype and gene expression of prostate stromal cells from patients of varying ages and their influence on tumour formation by prostate epithelial cells.
abstract: Prostate cancer (PCa) is an age-related disease, and the stromal microenvironment plays an important role in prostatic malignant progression. However, the differences in prostate stromal cells present in young and old tissue are still obscure. We established primary cultured stromal cells from normal prostatic peripheral zone (PZ) of donors of varying ages and found that cultured stromal cells from old donors (PZ-old) were more enlarged and polygonal than those from young donors (PZ-young). Furthermore, based on immunocytochemical and ultrastructural analysis, the components of stromal cells changed from a majority of fibroblasts to a mixture of fibroblasts and myofibroblasts with increasing donor age. Using a three-dimensional in vitro culture system, we found that PZ-old stromal cells could enhance the proliferation, migration and invasion of cocultured benign BPH-1 and PC-3 cells. Using an in vivo tissue recombination system, we also found that PZ-old stromal cells are more effective than PZ-young cells in promoting tumour formation by BPH-1 cells of high passage (>100) and PC-3 cells. To probe the possible mechanism of these effects, we performed cDNA microarray analysis and profiled 509 upregulated genes and 188 downregulated genes in PZ-old cells. Among the changed genes, we found genes coding for a subset of paracrine factors that are capable of influencing adjacent epithelial cells; these include hepatocyte growth factor (HGF), fibroblast growth factor 5 (FGF5), insulin-like growth factor 2 (IGF2), insulin-like growth factor-binding protein 4 (IGFBP4), IGFBP5 and matrix metallopeptidase 1 (MMP1). Changes in the expression of these genes were further confirmed by quantitative real-time polymerase chain reaction (PCR), Western blotting and enzyme-linked immunosorbent assays. Overall, our findings indicate that stromal cells from prostate PZ of old donors are more active than similar cells from young donors in promoting the malignant process of adjacent epithelial cells. This finding hints at a new potential strategy for the prevention of PCa.
authors.affiliation: Department of Urology, The Affiliated First People's Hospital of Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China.
authors.forename: Yong-Chuan
authors.initials: YC
authors.lastname: Wang
authors.forename: Sheng-Qiang
authors.initials: SQ
authors.lastname: Yu
authors.forename: Xiao-Hai
authors.initials: XH
authors.lastname: Wang
authors.forename: Bang-Min
authors.initials: BM
authors.lastname: Han
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Zhao
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Hong
authors.forename: Shu-Jie
authors.initials: SJ
authors.lastname: Xia
mesh_terms: D000367:Age Factors; D000818:Animals; D001483:Base Sequence; D018920:Coculture Techniques; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure
chemical_list: D017931:DNA Primers