Neuroepithelial interactions in prostate cancer are enhanced in the presence ofprostatic stroma

Cornell, Robert J.; Rowley, David R.; Wheeler, Thomas M.; Ali, Najeeba; Ayala, Gustavo

doi:10.1016/s0090-4295(02)02426-3

Cited by 42 publications

(26 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has also been shown that stromal PSCs may play a regulatory role in the interaction between cancer cells and nerves (40,41). It has been reported (42) that immortalized human PSC lines secrete NGF when stimulated by TGFb, and the supernatants of hPSC strongly stimulated neurite outgrowth (11).…”

Section: Discussionmentioning

confidence: 99%

Sonic Hedgehog Paracrine Signaling Activates Stromal Cells to Promote Perineural Invasion in Pancreatic Cancer

Zheng

et al. 2014

Clinical Cancer Research

136

113

View full text Add to dashboard Cite

Purpose: Pancreatic cancer is characterized by stromal desmoplasia and perineural invasion (PNI). We sought to explore the contribution of pancreatic stellate cells (PSC) activated by paracrine Sonic Hedgehog (SHH) in pancreatic cancer PNI and progression.Experimental Design: In this study, the expression dynamics of SHH were examined via immunohistochemistry, real-time PCR, and Western blot analysis in a cohort of carcinomatous and nonneoplastic pancreatic tissues and cells. A series of in vivo and in vitro assays was performed to elucidate the contribution of PSCs activated by paracrine SHH signaling in pancreatic cancer PNI and progression.Results: We show that SHH overexpression in tumor cells is involved in PNI in pancreatic cancer and is an important marker of biologic activity of pancreatic cancer. Moreover, the overexpression of SHH in tumor cells activates the hedgehog pathway in PSCs in the stroma instead of activating tumor cells. These activated PSCs are essential for the promotion of pancreatic cancer cell migration along nerve axons and nerve outgrowth to pancreatic cancer cell colonies in an in vitro three-dimensional model of nerve invasion in cancer. Furthermore, the coimplantation of PSCs activated by paracrine SHH induced tumor cell invasion of the trunk and nerve dysfunction along sciatic nerves and also promoted orthotropic xenograft tumor growth, metastasis, and PNI in in vivo models.Conclusions: These results establish that stromal PSCs activated by SHH paracrine signaling in pancreatic cancer cells secrete high levels of PNI-associated molecules to promote PNI in pancreatic cancer. Clin Cancer Res; 20(16); 4326-38. Ó2014 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

Sonic Hedgehog Paracrine Signaling Activates Stromal Cells to Promote Perineural Invasion in Pancreatic Cancer

Zheng

et al. 2014

Clinical Cancer Research

136

113

View full text Add to dashboard Cite

show abstract

“…Perineural invasion (PNI), commonly found in PCa, is a hosttumor interaction between nerves and cancer cells that leads to costimulation of growth. [22][23][24][25][26] Cancer cells grow more when around the nerve and also induce neurogenesis in an autocrine loop. 27 We previously demonstrated that PNI diameter, a measure of tumor diameter around the nerve, is also a very strong biomarker for BCR-free survival.…”

mentioning

confidence: 99%

Determining Prostate Cancer-Specific Death through Quantification of Stromogenic Carcinoma Area in Prostatectomy Specimens

Ayala

Müezzínoğlu

Hammerich

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

We previously reported that reactive stroma grading in prostate cancer (PCa) is predictive of biochemical recurrence in prostatectomies and biopsies. In this study, we tested whether quantifying the percentage of reactive stromal grade 3 (RSG 3; stromogenic carcinoma pattern) in the entire tumor is predictive of PCa-specific death. Whole-mount prostatectomies operated by a single surgeon obtained between 1983 and 1998 were reviewed. Reactive stroma was evaluated as described previously, and areas of RSG 3 in the entire tumor were registered as percentages of total tumor. Statistical analysis was performed using Spearman, Kaplan-Meier, and Cox analyses. In all, 872 cases were Prostate cancer (PCa) remains the most common malignancy affecting men and is the second-leading cause of cancer-related death of men in the United States. 1,2 The most accepted and internationally used histological classification to predict the behavior of PCa is the Gleason scoring system. 3-7 Tools such as the Kattan nomogram or the Partin tables combine predictive information to optimize the prediction of time to biochemical recurrence (BCR). 8 -11 However, all of these histological parameters examine the epithelial component of the cancer, and not the interaction between the tumor and the host.The most common histological interaction between the tumor and the native host stroma in many tumors is desmoplasia, or reactive stroma (RS). Reactive stroma in PCa was described in our previous studies and characterized at the phenotypic, 12-15 morphological, 16,17 and genomic levels. 18 We immunophenotyped RS as cells coexpressing vimentin and smooth muscle ␣-actin, with loss of terminal muscle differentiation markers such as desmin and/or calponin. Other studies described RS as a mixture of fibroblasts, myofibroblasts, endothelial cells, and immune cells in breast cancer. 19 -21 We recently demonstrated that RS is promising as a new marker to predict a patient's time to progression in PCa, using both biopsies and tissue microarrays from radical prostatectomy specimens. [12][13][14] To determine whether RS carries predictive information, we charac-

show abstract

“…21 In view of this, it would seem intuitive that widespread perineural invasion infiltration of large diameter nerves, and a close proximity of nerves showing perineural invasion to either the prostatic capsule or surgical excision margin may more frequently be associated with biochemical or clinical recurrence and thus have prognostic significance. This study was undertaken to investigate the association between detailed parameters of perineural invasion and biochemical failure in a consecutive series of radical prostatectomy specimens, and to compare these results with those obtained from assessment of established prognostic parameters for prostatic adenocarcinoma.…”

mentioning

confidence: 99%

Parameters of perineural invasion in radical prostatectomy specimens lack prognostic significance

et al. 2008

View full text Add to dashboard Cite

The prognostic significance of perineural invasion by prostate cancer is debated. We have evaluated the association between biochemical failure and measurements of perineural invasion in radical prostatectomy specimens. Perineural invasion was identified in sections using S-100 protein immunostaining. For nerves showing invasion, the involved nerve closest to the edge of the prostate and to the surgical excision margin, as well as the diameter of these nerves, the largest nerve showing perineural invasion and its proximity to the excision margin, and the percentage of nerves showing perineural invasion up to 1.75 mm from the excision margin was determined and tested against time to prostate-specific antigen failure, along with preoperative prostate-specific antigen levels, highest Gleason primary grade, Gleason score and TNM T category. Perineural invasion was present in 90% of cases, with extraprostatic perineural invasion in 25% of tumors. Diameter of nerves showing perineural invasion ranged from 11 to 680 lm and the shortest distance to the surgical excision margin ranged from 33 to 2.57 mm. Perineural invasion density ranged from 6 to 96%. Gleason scores were six in 58 cases, seven in 43 cases, eight in three cases and nine in one case. Clinical T categories were T1c in 75 cases, T2a in 22 cases, T2b in five cases, T2c in two cases, T3 in one case. During a follow-up period of 11 to 55 months (median 26 months), 27 patients showed prostate-specific antigen failure. On univariate analysis only presence of extraprostatic perineural invasion, among parameters of perineural invasion, showed a weak correlation with outcome, while on multivariate analysis this lost significance and preoperative prostatespecific antigen levels, Gleason score and excision margin status were independently associated with biochemical failure. We conclude that the investigated parameters of perineural invasion do not predict prostate-specific antigen recurrence in radical prostatectomy specimens.

show abstract

Neuroepithelial interactions in prostate cancer are enhanced in the presence ofprostatic stroma

Cited by 42 publications

References 24 publications

Sonic Hedgehog Paracrine Signaling Activates Stromal Cells to Promote Perineural Invasion in Pancreatic Cancer

Sonic Hedgehog Paracrine Signaling Activates Stromal Cells to Promote Perineural Invasion in Pancreatic Cancer

Determining Prostate Cancer-Specific Death through Quantification of Stromogenic Carcinoma Area in Prostatectomy Specimens

Parameters of perineural invasion in radical prostatectomy specimens lack prognostic significance

Contact Info

Product

Resources

About