Selective Interactions between Prostate Fibroblast and Epithelial Cells in Co-Culture Maintain the BPH Phenotype

Bayne, Colin W.; Ross, Margaret; Donnelly, Frank; Chapman, Karen; Buck, Colin; Bollina, Prasad; Habib, Fouad K.

doi:10.1159/000030274

Cited by 16 publications

(13 citation statements)

References 17 publications

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“…Efforts to model stromal and epithelial cell interactions in in vitro culture have helped elucidate the cross talk between cell types (Bayne et al 1998, Habib et al 2000. In vitro coculture studies have produced conflicting results of cell regulation.…”

Section: Cell Culture Models To Understand Ar Function and Cell Commumentioning

confidence: 99%

Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell's fault.

Arnold¹,

Isaacs²

2002

Endocrine-Related Cancer

184

135

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The acquisition of an androgen-independent phenotype by prostate cancer cells is presently a death sentence for patients. In order to have a realistic chance of changing this outcome, an understanding of what drives the progression to androgen independence is critical. We review here a working hypothesis based on the position that the development of androgen-independent epithelial cells is the result of a series of cellular and molecular events within the whole tissue that culminates in the loss of normal tissue-maintained growth control. This tissue includes the epithelial and stromal cells, the supporting extracellular matrix and circulating hormones. This review discusses the characteristics of these malignant cells, the role of stromal cells involved in growth and the differentiation of epithelial cells, and the role of the extracellular matrix as a mediator of the phenotypes of stromal and epithelial cells. In addition, environmental, neuroendocrine and immune factors that may contribute to disturbance of the fine balance of the epithelial-stromal-extracellular matrix connection are considered. While the goal of many therapeutic approaches to prostate cancer has been androgen ablation or targeting the androgen receptor (AR) of epithelial cells, these therapies become ineffective as the cells progress beyond dependence on androgen for growth control. Twenty years ago Sir David Smithers debated that cancer is the result of loss of tolerance within tissues and the organizational failure of normal growth-control mechanisms. This is precipitated by prolonged or abnormal demands for regeneration or repair, rather than of any inherent disorder peculiar to each of the individual components involved. He wrote 'It is not the cell itself that is disorderly, but its relationship with the rest of the tissue'. We have gained significantly large amounts of precise data on the effects of androgenic ablation on cancerous prostate cells and on the role of the AR in prostate cancer. The need has come to compile this information towards a perspective of dysregulation of tissue as a whole, and to develop experimental systems to address this broader perspective to find and develop therapies for treatment and prevention.

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Section: Cell Culture Models To Understand Ar Function and Cell Commumentioning

confidence: 99%

Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell's fault.

Arnold¹,

Isaacs²

2002

Endocrine-Related Cancer

184

135

View full text Add to dashboard Cite

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“…The addition of conditioned medium from stromal cell cultures and the presence of testosterone or dihydrotestosterone facilitates morphogenesis and the formation of luminal structures in Matrigel, the outer cells expressing high-molecular-weight cytokeratins (K1, 5, 10, and 14) and the inner cells expressing K18 (Lang et al 2001). Despite proper three-dimensional arrangement, expression of AR does not regenerate the entire transcriptional program and the in vivo response of androgen stimulation (Bayne et al 1998;Hudson et al 2000). Secretory differentiation and androgen responsiveness are only reliably achieved when human PECs are recombined with rat urogenital mesenchyme and implanted beneath the renal capsule of athymic mice (Hayward et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Regulation of cell proliferation in a stratified culture system of epithelial cells from prostate tissue

Gustafson

Grim

et al. 2006

Cell Tissue Res

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Mechanisms controlling epithelial proliferation and differentiation in the prostate have been primarily investigated in mouse models. The regulation of proliferation and differentiation is poorly understood in human prostate epithelial cells. In vivo, the glandular prostate epithelium consists of a p63-positive proliferating basal cell layer and a post-mitotic p27-positive secretory cell layer. We have established an organized stratified culture system of human primary prostate epithelial cells to gain insight into mechanisms regulating proliferation and differentiation. In this system, expression of p63 is observed in the bottom layer. In addition, BrdU incorporation persists even though cells are confluent. In contrast, in the upper layer, p63 expression is greatly diminished, p27 is expressed, and the cells are growth arrested. Overexpression of cyclin D1 or knockdown of p27 does not increase proliferation. After inactivation of the nuclear phosphoprotein Rb, the cell layers remain organized and cell proliferation increases only in the bottom layer. Furthermore, the expression of p63 remains confined to the bottom layer after Rb inactivation. Altogether, this in vitro model recapitulates certain aspects of in vivo growth regulation and differentiation and suggests that the loss of Rb family proteins in human cells trigger hyperplasia but is not sufficient for transformation.

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“…In an attempt to overcome this limitation, we chose a co-culture system of epithelial cells and fibroblasts from benign hyperplastic prostate tissues, employing a defined medium. A morphological study (8) on cells from BPH tissues demonstrated that when grown in co-culture, the epithelial cells exhibited round nuclei, tonofibrils, and microvilli, and the fibroblasts had elongated nuclei, large amounts of Golgi apparatus, and cilia; these are characteristics of the differentiated state. However, there were no studies using a co-culture model to examine differential gene expression in cells derived from BPH tissues.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of genes in co-cultured versus separately cultured fibroblasts and epithelial cells from human benign hyperplastic prostate tissues

Yang

Xuan²,

Mo³

et al. 2010

Int J Mol Med

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Abstract. The prostate is composed mainly of epithelial and stromal cells, whose dynamic interaction is vital to a broad array of cellular processes, including proliferation, differentiation, growth, and apoptosis. To understand intercellular communication in the development and progression of prostatic diseases, we examined gene expression in tissues from five patients diagnosed with benign prostatic hyperplasia (BPH). Fibroblasts and epithelial cells derived from these tissues were grown in a primary co-culture system that retains many characteristics of the intact human prostate. The mRNA levels of expressed genes as assessed by differential-display reverse transcription-PCR revealed that 110 genes were differentially expressed in co-cultured fibroblasts and epithelial cells, compared with expression in separately cultured cells. Eighty-four of these were confirmed by reverse Northern blotting, and 68 were successfully sequenced. Of the sequenced genes, 43 were differentially expressed in epithelial cells (37 upregulated, 6 downregulated), and 25 were differentially expressed in fibroblasts (6 upregulated, 19 downregulated) in co-cultures versus separate cultures. Semi-quantitative RT-PCR analysis of 12 genes with known functions showed that five of these were differentially expressed in co-cultured cells. Human kallikrein gene 7 (KLK7) was markedly upregulated in co-cultured compared with separately cultured epithelial cells (P<0.001), whereas S100 calcium binding protein A11, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, cyclin I, and latexin were significantly downregulated in co-cultured fibroblasts (P<0.05). Quantitative real-time RT-PCR and Western blot analysis confirmed KLK7 upregulation at both the mRNA and protein levels, respectively. Thus, epithelial-stromal cell interaction and communication are likely to be important in BPH. Epithelial cells and fibroblasts may interplay coordinately or collaboratively to influence cellular growth and death through dynamically differential gene expression in response to physiological and pathophysiological changes.

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Selective Interactions between Prostate Fibroblast and Epithelial Cells in Co-Culture Maintain the BPH Phenotype

Cited by 16 publications

References 17 publications

Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell's fault.

Mechanisms involved in the progression of androgen-independent prostate cancers: it is not only the cancer cell's fault.

Regulation of cell proliferation in a stratified culture system of epithelial cells from prostate tissue

Differential expression of genes in co-cultured versus separately cultured fibroblasts and epithelial cells from human benign hyperplastic prostate tissues

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