scholarly journals Overexpression of FGF9 in Prostate Epithelial Cells Augments Reactive Stroma Formation and Promotes Prostate Cancer Progression

2015 ◽  
Vol 11 (8) ◽  
pp. 948-960 ◽  
Author(s):  
Yanqing Huang ◽  
Chengliu Jin ◽  
Tomoaki Hamana ◽  
Junchen Liu ◽  
Cong Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Reactive Stroma ◽  
Prostate Epithelial Cells

Modulating tumor reactive stroma by extracorporeal shock waves to control prostate cancer progression

The Prostate ◽  
2020 ◽  
Vol 80 (13) ◽  
pp. 1087-1096
Author(s):  
Letizia Rinella ◽  
Benedetta Pizzo ◽  
Roberto Frairia ◽  
Luisa Delsedime ◽  
Giorgio Calleris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Shock Waves ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Reactive Stroma ◽  
Extracorporeal Shock Waves

scholarly journals Reducing Selenoprotein F Promotes the Transformation of Immortalized Prostate Epithelial Cells

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1809-1809
Author(s):  
Lenny Hong ◽  
Mostafa Elhodaky ◽  
Shrinidhi Kadkol ◽  
Alan Diamond
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Cancer Progression ◽  
Tca Cycle ◽  
Soft Agar ◽  
Metabolic Shift ◽  
Normal Prostate ◽  
Funding Sources ◽  
Prostate Cells ◽  
Prostate Epithelial Cells

Abstract Objectives Selenoprotein F (SELENOF) levels are responsive to available dietary selenium and found in high levels in benign prostate cells. It is implicated in prostate cancer (PCa) mortality due to associations between polymorphisms in the corresponding gene and death from the disease. SELENOF levels are dramatically lower in prostate cancer compared to adjacent benign tissue. The objective of this study was to determine whether reducing SELENOF levels in human, non-transformed RWPE-1 prostate epithelial cells alters their phenotype to implicate SELENOF loss in PCa progression. Methods SELENOF levels were reduced in RWPE-1 cells that express high levels of SELENOF using a SELENOF shRNA construct. Proliferation was determined by quantifying DNA using fluorometric dsDNA quantitation. Growth in soft agar and cell mobility of cells in culture (wound healing assay) were imaged using an Evos FL microscope and quantified using Image J software. The oxygen consumption rate (OCR) was measured using a Seahorse XFe24 Analyzer. Results SELENOF levels were reduced in RWPE-1 and these cells exhibited decreased contact inhibition in culture (n = 3, P < 0.001) when compared to controls. Normal prostate epithelial cells are atypical in that they rely on glycolysis for energy production, have a truncated TCA cycle, and a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) occurs in PCa. Reducing SELENOF in RWPE-1 cells resulted in higher OCR compared to controls, indicating that SELENOF can impact the sources and pathways used in cellular energy metabolism. Conclusions Reduced SELENOF levels in RWPE-1 prostate cells resulted in properties consistent with a transformed phenotype and an increase in OCR, and indicating that the reduction in SELENOF may contribute a metabolic shift towards a PCa cancer-like metabolism. Together, these results indicate that SELENOF loss likely contributes to cancer progression. Funding Sources This work was supported by a grant from the Department of Defense to AMD and a Pre-Doctoral Education for Clinical and Translational Scientists Fellowship to LKH.

REACTIVE STROMA IN PROSTATE CANCER PROGRESSION

2001 ◽  
Vol 166 (6) ◽  
pp. 2472-2483 ◽  
Author(s):  
JENNIFER A. TUXHORN ◽  
GUSTAVO E. AYALA ◽  
DAVID R. ROWLEY
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Reactive Stroma

scholarly journals Transcriptional network involving ERG and AR orchestrates Distal-Less Homeobox 1 mediated prostate cancer progression

2020 ◽  
Author(s):  
Sakshi Goel ◽  
Vipul Bhatia ◽  
Shannon Carskadon ◽  
Nilesh Gupta ◽  
Mohammad Asim ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Gene Fusion ◽  
Transcriptional Regulators ◽  
Tumor Burden ◽  
Prostate Cancer Progression ◽  
Poor Survival ◽  
Aggressive Disease ◽  
Functional Assays ◽  
Prostate Epithelial Cells

Abstract Nearly half of the prostate cancer (PCa) cases show elevated levels of ERG oncoprotein due to TMPRSS2-ERG gene fusion. Here, we demonstrate ERG mediated upregulation of Distal-less homeobox-1 (DLX1), an established PCa biomarker. Using series of functional assays, we show DLX1 elicits oncogenic properties in prostate epithelial cells, and abrogating its function leads to reduced tumor burden in mouse xenografts. Clinically, ~60% of the PCa patients exhibit high DLX1 levels, while ~50% of these cases also harbor elevated ERG associated with aggressive disease and poor survival probability. Mechanistically, we show that ERG gets recruited onto DLX1 promoter and interacts with its enhancer-bound androgen receptor (AR) and FOXA1 to regulate DLX1 expression in TMPRSS2-ERG positive cases. Alternatively, in ERG-negative cases, DLX1 is regulated by AR/AR-V7 and FOXA1. Importantly, BET bromodomain inhibitors disrupt the transcriptional regulators of DLX1 and its associated oncogenic properties, signifying their efficacy in treatment of DLX1-positive PCa patients.

scholarly journals The reactive stroma microenvironment and prostate cancer progression

2012 ◽  
Vol 19 (6) ◽  
pp. R187-R204 ◽  
Author(s):  
David A Barron ◽  
David R Rowley
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cancer Progression ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tissue Growth ◽  
Prostate Cancer Progression ◽  
Prostate Tumorigenesis ◽  
Reactive Stroma

Reactive stroma initiates during early prostate cancer development and coevolves with prostate cancer progression. Previous studies have defined the key markers of reactive stroma and have established that reactive stroma biology influences prostate tumorigenesis and progression. The stem/progenitor cells of origin and the mechanisms that regulate their recruitment and activation to myofibroblasts or carcinoma-associated fibroblasts are essentially unknown. Key regulatory factors have been identified, including transforming growth factor β, interleukin-8, fibroblast growth factors, connective tissue growth factor, wingless homologs-Wnts, and stromal cell-derived factor-1, among others. The biology of reactive stroma in cancer is similar to the more predictable biology of the stroma compartment during wound repair at sites where the epithelial barrier function is breached and a stromal response is generated. The coevolution of reactive stroma and the biology of how reactive stroma–carcinoma interactions regulate cancer progression and metastasis are targets for new therapeutic approaches. Such approaches are strategically designed to inhibit cancer progression by uncoupling the reactive stroma niche.

scholarly journals Transcriptional network involving ERG and AR orchestrates Distal-Less Homeobox 1 mediated prostate cancer progression

2020 ◽  
Author(s):  
Sakshi Goel ◽  
Vipul Bhatia ◽  
Shannon Carskadon ◽  
Nilesh Gupta ◽  
Mohammad Asim ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Gene Fusion ◽  
Transcriptional Regulators ◽  
Tumor Burden ◽  
Prostate Cancer Progression ◽  
Poor Survival ◽  
Aggressive Disease ◽  
Functional Assays ◽  
Prostate Epithelial Cells

AbstractNearly half of the prostate cancer (PCa) cases show elevated levels of ERG oncoprotein due to TMPRSS2-ERG gene fusion. Here, we demonstrate ERG mediated upregulation of Distal-less homeobox-1 (DLX1), an established PCa biomarker. Using series of functional assays, we show DLX1 elicits oncogenic properties in prostate epithelial cells, and abrogating its function leads to reduced tumor burden in mouse xenografts. Clinically, ∼60% of the PCa patients exhibit high DLX1 levels, while ∼50% of these cases also harbor elevated ERG associated with aggressive disease and poor survival probability. Mechanistically, we show that ERG gets recruited onto DLX1 promoter and interacts with its enhancer-bound androgen receptor (AR) and FOXA1 to regulate DLX1 expression in TMPRSS2-ERG positive cases. Alternatively, in ERG-negative cases, DLX1 is regulated by AR/AR-V7 and FOXA1. Importantly, BET bromodomain inhibitors disrupt the transcriptional regulators of DLX1 and its associated oncogenic properties, signifying their efficacy in treatment of DLX1-positive PCa patients.

scholarly journals Stromal Reactivity Differentially Drives Tumor Cell Evolution and Prostate Cancer Progression

2017 ◽  
Author(s):  
Ziv Frankenstein ◽  
David Basanta ◽  
Omar E. Franco ◽  
Yan Gao ◽  
Rodrigo A. Javier ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Evolutionary Dynamics ◽  
Multiscale Model ◽  
Cell Behavior ◽  
Tumor Evolution ◽  
Tumor Aggressiveness ◽  
Prostate Cancer Progression ◽  
Reactive Stroma ◽  
Clinical Biomarkers

AbstractWe implemented a hybrid multiscale model of carcinogenesis that merges data from biology and pathology on the microenvironmental regulation of prostate cancer (PCa) cell behavior. It recapitulates the biology of stromal influence in prostate cancer progression. Our data indicate that the interactions between the tumor cells and reactive stroma shape the evolutionary dynamics of PCa cells and explain overall tumor aggressiveness. We show that the degree of stromal reactivity, when coupled with the current clinical biomarkers, significantly improves PCa prognostication, both for death and recurrence, that may alter treatment decisions. We also show that stromal reactivity correlates directly with tumor growth but inversely modulates tumor evolution. This suggests that the aggressive stromal independent PCa may be an inevitable evolutionary result of poor stromal reactivity. It also suggests that purely tumor centric metrics of aggressiveness may be misleading in terms on clinical outcome.

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