New targets for therapy in prostate cancer: modulation of stromal–epithelial interactions

Chung, Leland W.K.; Hsieh, Chia Ling; Law, Andrew M. K.; Sung, Shian Ying; Gardner, Thomas A.; Egawa, Masayuki; Matsubara, Shigeji; Zhau, Haiyen E.

doi:10.1016/s0090-4295(03)00796-9

Cited by 53 publications

(35 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[71][72][73][74] However, these effects are mainly thought to be mediated by the expression of cytokines and growth factors by the cancer-associated fibroblasts/inflammatory cells and it is unlikely that the proliferative activity of these cells per se has a significant role in these processes. We are aware that the ultimate test to determine whether the low-grade carcinomas with cellular, proliferative stroma and increased Recurrence Score do worse than those without these features would be longterm patient outcome.…”

Section: Discussionmentioning

confidence: 99%

A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas

et al. 2012

View full text Add to dashboard Cite

Oncotype DX is an RT-PCR-based 21-gene assay validated to provide prognostic and predictive information in the form of a Recurrence Score in patients with estrogen receptor-positive, lymph node-negative breast cancer. Although the Recurrence Score was shown to correlate with several histopathological tumor features, there is a significant proportion of cases showing an apparent discrepancy between Recurrence Score and risk estimates based on the traditional clinicopathological tumor features. In this study, we tested whether a proliferating, cellular stroma and/or admixed inflammatory cells may result in an artificially increased Recurrence Score in low-grade invasive breast cancers. We analyzed the histopathological features in 141 low-grade invasive breast carcinomas, including 41 special type (tubular, cribriform and mucinous) carcinomas, with available Recurrence Score. The tumor stroma was evaluated for increased cellularity and presence of inflammatory cells. Double immunohistochemical stains for pancytokeratin and Ki-67 was performed to assess the cell proliferation in tumor vs stromal/inflammatory cells. The clinicopathological features of tumors with Recurrence Score o18 (low risk) were compared with those with Recurrence Score Z18 (intermediate/high risk). Carcinomas associated with Recurrence Score Z18 showed lower progesterone receptor immunoreactivity, increased stromal cellularity and presence of inflammatory cells associated with the tumor. Double immunohistochemical stains showed significantly increased proliferation in stromal/inflammatory cells compared with carcinoma cells in cases associated with Recurrence Score Z18. A Ki-67-positive stromal/ tumor cells ratio of 41 predicted Recurrence Score Z18 with an area under the curve of 0.8967 on receiver operator curve analysis (Po0.0001). Our results suggest that the presence of increased stromal cellularity and/ or associated inflammatory cells in low-grade invasive breast carcinomas may contribute to an apparently increased risk of recurrence according to Oncotype DX Recurrence Score. Careful assessment and correlation with histopathological features in such cases may help in determining the appropriate patient management.

show abstract

Section: Discussionmentioning

confidence: 99%

A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas

et al. 2012

View full text Add to dashboard Cite

show abstract

“…BPH is not a precursor for CaP, other precursor lesions are recognised and are discussed below. Current therapeutic options for CaP remain inadequate (Chung et al, 2003). While tumours initially respond well to androgen reduction, the duration of response is short, typically 12-33 months.…”

Section: The Prostate Gland and Pathologymentioning

confidence: 99%

“…Other actions include transdifferentiation of fibroblasts to myofibroblasts, and induction of extracellularmatrix components such as collagen, fibronectin, thrombospondin, osteopontin, osteonectin, elastin and protease inhibitors by cancer cells (Chung et al, 2003). These factors are especially important for the survival of metastatic cancer cells in bone.…”

Section: 2a Transforming Growth Factor  (Tgf)mentioning

confidence: 99%

“…In desmoplastic tumours the stromal compartment can increase in size, reaching up to 90% (Brennen et al, 2006). Stromal cells alter the tumorigenic and metastatic potential of prostate epithelium and the characteristic reactive stroma emerges (Chung et al, 2003). There is also a loss of normal tissue architecture, nuclear atypia, genetic alterations, loss of tissue boundaries, and angiogenesis (Cunha et al, 2003).…”

Section: Cancer Reactive Stromamentioning

confidence: 99%

See 1 more Smart Citation

Androgen receptor signalling in prostate: Effects of stromal factors on normal and cancer stem cells

Berry

Maitland

Collins

2008

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Please cite this article as: Berry, P.A., Maitland, N.J., Collins, A.T., Androgen receptor signalling in prostate: effects of stromal factors on normal and cancer stem cells, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe prostate gland is the most common site for cancer in males within the developed world. Androgens play a vital role in prostate development, maintenance of tissue function and pathogenesis of prostate disease. The androgen receptor signalling pathway facilitates that role in both the epithelial compartment and in the underlying stroma. Stroma is a key mediator of androgenic effects upon the epithelium and can regulate both the fate of the epithelial stem cell and potentially the initiation and progression of prostate cancer. Different groups of growth factors are expressed by stroma, which control proliferation, and differentiation of prostate epithelium demonstrating a critical role for stroma in epithelial growth and homeostasis. Paracrine stromal proteins may offer the possibility to control tumour stem cell growth and could permit prostate-specific targeting of both therapies and of androgenresponsive proteins. The effect of 5-dihydrotestosterone, the more potent metabolite of testosterone, on expression of androgen regulated genes in stroma from benign prostatic hyperplasia is a key mediator of epithelial cell fate. Global gene expression arrays have recently identified new candidate genes in androgen responsive stroma, some of which have androgen receptor binding sites in their promoter regions. Some of these genes have direct androgen receptor binding ability.

show abstract

“…Agents such as the specific androgen receptor modulators (sARMs) and an adenoviral-osteocalcin promoter vector could be used to target both cancer cells and the stromal-epithelial interaction, with targeting of both elements simultaneously representing a unique approach to localised and metastatic cancer therapy. 30 Cadherins They are a class of cell adhesion molecule that maintain epithelial tissue differentiation and structural integrity. A study by Umbas et al showed that patients with aberrant E-cadherin staining of prostate cancer tumours had a significantly lower survival rate than patients with normal staining (Po0.001) at a mean follow-up of 36 months; 31 this difference was also evident after longer-term follow-up (Figure 1).…”

Section: Cancer Cell-host Relationshipsmentioning

confidence: 99%

Future opportunities for the diagnosis and treatment of prostate cancer

Watson

Schalken²

2004

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

Despite recent advances, current diagnostic tests and treatment of prostate cancer have limitations. In the last few years, numerous biomolecules have been investigated with the aim of improving diagnosis, including kallikrein-like proteases, growth factors and neuroendocrine markers. Analysis of susceptibility genes has also been a focus of attention. Extensive research into new therapeutic approaches is also underway, including targeting angiogenesis, immune regulation and stromal-epithelial interactions. Gene therapy, gene chip technology and proteomics have emerged as promising innovations. The host of novel diagnostic markers and therapies require appropriate validation, both phenotypical and functional. A further consideration is the need to re-evaluate clinical trial design and end points to facilitate progression of promising targets through the clinical trial process. Overall, the outlook for the treatment of prostate cancer looks promising, with any advances likely to require both a multimodal and multidisciplinary approach.

show abstract

New targets for therapy in prostate cancer: modulation of stromal–epithelial interactions

Cited by 53 publications

References 36 publications

A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas

A mitotically active, cellular tumor stroma and/or inflammatory cells associated with tumor cells may contribute to intermediate or high Oncotype DX Recurrence Scores in low-grade invasive breast carcinomas

Androgen receptor signalling in prostate: Effects of stromal factors on normal and cancer stem cells

Future opportunities for the diagnosis and treatment of prostate cancer

Contact Info

Product

Resources

About