Characterization of subepithelial interstitial cells in normal and pathological human prostate

Gevaert, Thomas; Lerut, Evelyne; Joniau, Steven; Franken, Jan; Roskams, Tania; Ridder, Dirk De

doi:10.1111/his.12402

Cited by 16 publications

(10 citation statements)

References 28 publications

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“…Wrapping cells are also fibroblast-like, and are tightly associated with the outer part of the smooth muscle layer, whereas interstitial fibroblasts are located between prostate ducts (Peng et al, 2013). In the case of the human prostate, ultrastructural analyses of subepithelial cells have resulted in their subdivision into fibroblasts, interstitial Cajal-like cells and spindle-shaped cells with myoid differentiation (Gevaert et al, 2014). Tissue recombination studies have suggested that the differentiation of smooth muscle cells from the UGM is regulated by signaling from the adjacent epithelium during organogenesis (Hayward et al, 1997).…”

Section: Stromal Progenitors and Differentiation During Prostate Devementioning

confidence: 99%

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

2017

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Prostate organogenesis is a complex process that is primarily mediated by the presence of androgens and subsequent mesenchyme-epithelial interactions. The investigation of prostate development is partly driven by its potential relevance to prostate cancer, in particular the apparent re-awakening of key developmental programs that occur during tumorigenesis. However, our current knowledge of the mechanisms that drive prostate organogenesis is far from complete. Here, we provide a comprehensive overview of prostate development, focusing on recent findings regarding sexual dimorphism, bud induction, branching morphogenesis and cellular differentiation.

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Section: Stromal Progenitors and Differentiation During Prostate Devementioning

confidence: 99%

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

2017

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“…Telocytes (TCs) were identified as a new cell type of the stromal space [1] (details at www.telocytes.com). TCs were described in the trachea and lungs [2][3][4][5], besides other important locations: heart [6][7][8][9], female reproductive system [10][11][12][13], skin [14,15], digestive system [16][17][18][19], liver [20], urinary tract [21,22], prostate [23,24], skeletal muscle and neuromuscular spindles [25,26], eye [27], etc. Ultrastructurally, TCs are defined and easily to distinguish by their extremely long telopodes (tens up to hundreds of micrometres), an alternation of podoms and podomeres.…”

Section: Introductionmentioning

confidence: 99%

Protein profiling of human lung telocytes and microvascular endothelial cells using iTRAQ quantitative proteomics

Zheng

Crețoiu

Yan

et al. 2014

J Cellular Molecular Medi

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Telocytes (TCs) are described as a particular type of cells of the interstitial space (www.telocytes.com). Their main characteristics are the very long telopodes with alternating podoms and podomers. Recently, we performed a comparative proteomic analysis of human lung TCs with fibroblasts, demonstrating that TCs are clearly a distinct cell type. Therefore, the present study aims to reinforce this idea by comparing lung TCs with endothelial cells (ECs), since TCs and ECs share immunopositivity for CD34. We applied isobaric tag for relative and absolute quantification (iTRAQ) combined with automated 2-D nano-ESI LC-MS/MS to analyse proteins extracted from TCs and ECs in primary cell cultures. In total, 1609 proteins were identified in cell cultures. 98 proteins (the 5th day), and 82 proteins (10th day) were confidently quantified (screened by two-sample t-test, P < 0.05) as up- or down-regulated (fold change >2). We found that in TCs there are 38 up-regulated proteins at the 5th day and 26 up-regulated proteins at the 10th day. Bioinformatics analysis using Panther revealed that the 38 proteins associated with TCs represented cellular functions such as intercellular communication (via vesicle mediated transport) and structure morphogenesis, being mainly cytoskeletal proteins and oxidoreductases. In addition, we found 60 up-regulated proteins in ECs e.g.: cell surface glycoprotein MUC18 (15.54-fold) and von Willebrand factor (5.74-fold). The 26 up-regulated proteins in TCs at 10th day, were also analysed and confirmed the same major cellular functions, while the 56 down-regulated proteins confirmed again their specificity for ECs. In conclusion, we report here the first extensive comparison of proteins from TCs and ECs using a quantitative proteomics approach. Our data show that TCs are completely different from ECs. Protein expression profile showed that TCs play specific roles in intercellular communication and intercellular signalling. Moreover, they might inhibit the oxidative stress and cellular ageing and may have pro-proliferative effects through the inhibition of apoptosis. The group of proteins identified in this study needs to be explored further for the role in pathogenesis of lung disease.

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“…It was demonstrated that diverse stromal cell types with distinct phenotypes reside in the subepithelial area in the human prostate . We next explored the exact PD‐L1 + cell type in the TME.…”

Section: Resultsmentioning

confidence: 99%

“…A rabbit monoclonal PD‐L1 antibody (clone E1L3N) was investigated for use in immunohistochemistry (IHC). Markers for stromal cells were previously described to characterize the morphology and phenotype of subepithelial interstitial cells in prostate stroma: Vimentin, α‐SMA, CD34 and pan neuron marker protein gene product 9.5 (PGP9.5) . For tumor‐associated lymphocytes (TALs), we labeled tissue slides for FoxP3, CD3 and CD8 to highlight different lymphocyte subsets, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Co-localization of PD-L1 with PGP9.5 in prostate cancer TME It was demonstrated that diverse stromal cell types with distinct phenotypes reside in the subepithelial area in the human prostate. 23 We next explored the exact PD-L1 + cell type in the TME. To this end, we used IF double-staining to further characterize the population of PD-L1 + stromal component.…”

Section: Specificity Of Anti-pd-l1 Antibody Validationmentioning

confidence: 99%

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Expression of PD‐L1 in tumor‐associated nerves correlates with reduced CD8⁺ tumor‐associated lymphocytes and poor prognosis in prostate cancer

Han

Liang

et al. 2019

Intl Journal of Cancer

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To investigate immune profile consisting of stromal PD‐L1 expression, inhibitory or non‐T‐cell inflamed tumor microenvironment that may predict response to anti‐PD‐L1/PD‐1 immunotherapy in prostate cancer, we validated the specificity of a PD‐L1 monoclonal antibody (E1L3N) and identified PD‐L1 specific expression in prostatic stromal nerve cells. PD‐L1 expression was analyzed in 73 primary prostate cancers and 7 castration‐resistant prostate cancers (CRPC) by immunohistochemistry (IHC) and resulting data from primary prostate cancers were correlated with tumor‐associated lymphocytes (TALs), clinicopathological characteristics and clinical outcome. PD‐L1 was expressed in the tumor cells in only one primary prostate cancer case and none of the CRPC. However, PD‐L1 was frequently observed in the nerve branches in the tumor‐associated stroma (69 of 73 cases, 94.5%), supported by colocalization with axonal marker PGP9.5. FoxP3‐, CD3‐ and CD8‐positive T lymphocytes were observed in 74.6% (47/63), 98.4% (62/63) and 100% (61/61) of the cases, respectively. The density of PD‐L1+ tumor‐associated nerves (TANs) was inversely correlated with that of CD8+ TALs. Higher density of PD‐L1+ TANs was significantly associated with biochemical recurrence (BCR) in Kaplan–Meier survival analysis (p = 0.016). In both univariate and multivariate Cox analysis, the density of PD‐L1+ TANs was independently prognostic of BCR. In conclusion, PD‐L1 expression is rare in prostate tumor cells but prevalent in TANs and negatively correlated with CD8+ TALs. Neuro‐immunological interaction may be a contribution to immune‐suppressive microenvironment. Combinatorial treatment regimen designs to neural PD‐L1 and TALs should be warranted in future clinical application of anti‐PD‐L1/PD‐1 immunotherapy in prostate cancer.

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Characterization of subepithelial interstitial cells in normal and pathological human prostate

Abstract: The present study shows for the first time that the SE area in the human prostate houses different stromal cell types with distinct phenotypes. In BPH and PCa specific disease-related changes were observed in the organization and phenotypes of SE interstitial cells.

Cited by 16 publications

References 28 publications

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

Protein profiling of human lung telocytes and microvascular endothelial cells using iTRAQ quantitative proteomics

Expression of PD‐L1 in tumor‐associated nerves correlates with reduced CD8⁺ tumor‐associated lymphocytes and poor prognosis in prostate cancer

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Characterization of subepithelial interstitial cells in normal and pathological human prostate

Abstract: The present study shows for the first time that the SE area in the human prostate houses different stromal cell types with distinct phenotypes. In BPH and PCa specific disease-related changes were observed in the organization and phenotypes of SE interstitial cells.

Cited by 16 publications

References 28 publications

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

Prostate organogenesis: tissue induction, hormonal regulation and cell type specification

Protein profiling of human lung telocytes and microvascular endothelial cells using iTRAQ quantitative proteomics

Expression of PD‐L1 in tumor‐associated nerves correlates with reduced CD8+ tumor‐associated lymphocytes and poor prognosis in prostate cancer

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Expression of PD‐L1 in tumor‐associated nerves correlates with reduced CD8⁺ tumor‐associated lymphocytes and poor prognosis in prostate cancer