The role of the stromal microenvironment in prostate cancer

Condon, Mark S.

doi:10.1016/j.semcancer.2004.08.002

Cited by 77 publications

(69 citation statements)

References 42 publications

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“…AR in stromal cells: a stimulator for tumor progression and metastasis Stromal-epithelial interaction remains important for tumor progression and metastasis (Cunha et al, 2003;Bhowmick and Moses, 2005;Condon, 2005). During tumor progression, the stromal cells, including fibroblasts, myofibroblasts, endothelial, and immune cells, form a AR dual functions in prostate cancer therapy Y Niu et al microenvironment supporting the progression, survival, and metastasis of the tumor.…”

Section: Ar Dual Functions In Prostate Cancer Progression and Metastasismentioning

confidence: 99%

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

et al. 2010

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Prostate cancer is one of the major causes of cancerrelated death in the western world. Androgen-deprivation therapy (ADT) for the suppression of androgens binding to the androgen receptor (AR) has been the norm of prostate cancer treatment. Despite early success to suppress prostate tumor growth, ADT eventually fails leading to recurrent tumor growth in a hormonerefractory manner, even though AR remains to function in hormone-refractory prostate cancer. Interestingly, some prostate cancer survivors who received androgen replacement therapy had improved quality of life without adverse effect on their cancer progression. These contrasting clinical data suggest that differential androgen/ AR signals in individual cells of prostate tumors can exist in the same or different patients, and may be used to explain why ADT of prostate cancer fails. Such a hypothesis is supported by the results obtained from transgenic mice with selective knockout of AR in prostatic stromal vs epithelial cells and orthotopic transplants of various human prostate cancer cell lines with AR overexpression or knockout. These studies concluded that AR functions as a stimulator for prostate cancer proliferation and metastasis in stromal cells, as a survival factor of prostatic cancer epithelial luminal cells, and as a suppressor for prostate cancer basal intermediate cell growth and metastasis. These dual yet opposite functions of the stromal and epithelial AR may challenge the current ADT to battle prostate cancer and should be taken into consideration when developing new AR-targeting therapies in selective prostate cancer cells.

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Section: Ar Dual Functions In Prostate Cancer Progression and Metastasismentioning

confidence: 99%

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

et al. 2010

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“…12,13 Many research groups have also shown that a dynamic stromal-epithelial interaction plays a critical role in the progression and metastasis of PCa. [14][15][16][17][18][19][20] Growth factors play a central role in mediating the interactions between epithelial and stromal cells. 21 The stromal-epithelial interaction is also critical for mediating the effects of these molecules on epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

Jiang

Han²,

Zhao³

et al. 2011

Asian J Androl

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It is well known that prostate cancer (PCa) occurs predominantly in the peripheral zone (PZ), whereas benign prostatic hyperplasia (BPH) typically develops in the transition zone. To identify possible mechanisms underlying zonal differences, we compared the effects of prostate stromal cells derived from the peripheral zone (PZsc) and the transition zone (TZsc) on a PCa epithelial cell line (PC3) in the presence of sex hormones. First, we observed that androgen receptor (AR) mRNA was more highly expressed in PZsc than TZsc when the cells were treated with dihydrotestosterone (DHT) and b-oestradiol (E2) (P,0.05). By ELISA, we looked for differences in the secretion of peptide growth factors from PZsc and TZsc. We found that keratinocyte growth factor (KGF) secretion increased with increasing concentrations of DHT (P,0.01) and was higher in PZsc than TZsc. Under treatment with DHT plus E2, PZsc secreted more transforming growth factor-b1 (TGF-b1) than TZsc, but this pattern was reversed when the cells were treated with E2 only. With increasing concentrations of DHT, insulin-like growth factor-1 (IGF-1) secretion increased in PZsc but decreased in TZsc. To further characterize the effects of PZsc and TZsc on PC3 cells, we developed a coculture model and performed MTT assays, Western blot analysis and real-time RT-PCR. We found that PZsc promoted PC3 cell proliferation and progression better than TZsc, particularly when treated with 10 nmol l 21 DHT plus 10 nmol l 21 E2. In conclusion, our data suggest that PZsc may have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. These findings provide possible mechanisms underlying zonal differences in prostate diseases, which may aid the search for novel therapeutic targets for PCa.

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“…While prostate adenocarcinoma is ultimately an epithelial disease, it is widely accepted that the stroma is involved in initiating, maintaining, and promoting a malignant phenotype through inter-cell signaling (37,38). These processes may also occur in TAHN tissues, as shown by Hanson and colleagues, who have reported promoter methylation for GSTP1, RARß2 and CD44 in stromal cells associated with tumors (39).…”

Section: Discussionmentioning

confidence: 94%

Differential gene expression in tumor adjacent histologically normal prostatic tissue indicates field cancerization

Haaland

Heaphy²,

Butler³

et al. 2009

Int J Oncol

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Abstract. Field cancerization denotes the occurrence of aberrant cells in tumor adjacent histologically normal tissues (TAHN). To characterize field cancerization in prostate cancer, we used RNA from paired patient tumor and TAHN tissues excised at 1 cm from the tumor margin and subjected them to microarray expression analysis comparative to RNA from normal cancer-free prostatic tissues. Eleven novel transcripts were significantly up-regulated in TAHN tissues and also in tumors. Expression of early growth response protein 1, tristetraprolin, testican, and fatty acid synthase, mutually up-regulated at different levels in tumors and TAHN tissues was confirmed by quantitative reverse transcriptase PCR in the experimental and in an independent validation set. This study offers proof of expressional changes in field cancerized prostatic TAHN tissues at defined distances from tumor margins. Markers of field cancerized prostatic tissues could be early diagnostic indicators in biopsies after abnormal prostate-specific antigen and digital rectal examination and independent of cancerous histology and/or early targets for chemo-preventive intervention in pre-malignant disease.

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The role of the stromal microenvironment in prostate cancer

Cited by 77 publications

References 42 publications

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

The differential effects of prostate stromal cells derived from different zones on prostate cancer epithelial cells under the action of sex hormones

Differential gene expression in tumor adjacent histologically normal prostatic tissue indicates field cancerization

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