scholarly journals The role of inhibins and activins in prostate cancer pathogenesis.

2000 ◽  
pp. 243-256 ◽  
Author(s):  
C R Dowling ◽  
G P Risbridger
Keyword(s):  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Prostate Gland ◽  
Prostate Carcinogenesis ◽  
Cancer Pathogenesis ◽  
Number Of Patients ◽  
Related Proteins

Successful prostate cancer diagnosis and management continue to provide challenges for the clinician. While interventions aimed at the containment of both early and late disease continue to fail in a significant number of patients, the search for answers must incorporate an analysis of the processes of normal and aberrant growth and development within the gland itself. Inhibin and its structurally related protein, activin, are members of the transforming-growth-factor beta (TGFbeta) superfamily. Originally identified as regulators of FSH, these proteins are now recognised to have widespread biological functions. This might be expected of proteins that are structurally homologous to TGFbeta itself, which is recognised to have regulatory roles in both normal and malignant prostate tissue. The aim of this review is to examine the relationship between inhibins, activins and their related proteins and the development of prostate cancer. The homology with TGF, the pluripotent effects of activin on various tissues and the roles for inhibins in ovarian cancer make activins and inhibins candidate growth factors for involvement at multiple sites in the progression from benign disease to cancer. In compiling this review, we aim to delineate the changes in inhibins and activins in this pathway and in doing so implicate their potential roles in the progression of carcinogenesis. We will compare the changes in inhibin and its related proteins in prostate cancer to those that are known in ovarian cancer. We will discuss the similarities and differences between the putative role of activins and TGFbeta in prostate carcinogenesis. The importance of this review lies in demonstrating that inhibin, an endocrine hormone, and its related proteins may contribute to endocrine-related cancers, such as that of the prostate gland.

Inhibin/activin and ovarian cancer.

2004 ◽  
Vol 11 (1) ◽  
pp. 35-49 ◽  
Author(s):  
D M Robertson ◽  
H G Burger ◽  
P J Fuller
Keyword(s):  
Ovarian Cancer ◽  
Granulosa Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Alpha Subunit ◽  
Beta Subunits ◽  
Granulosa Cell Tumours

Inhibin and activin are members of the transforming growth factor beta (TGFbeta) family of cytokines produced by the gonads, with a recognised role in regulating pituitary FSH secretion. Inhibin consists of two homologous subunits, alpha and either betaA or betaB (inhibin A and B). Activins are hetero- or homodimers of the beta-subunits. Inhibin and free alpha subunit are known products of two ovarian tumours (granulosa cell tumours and mucinous carcinomas). This observation has provided the basis for the development of a serum diagnostic test to monitor the occurrence and treatment of these cancers. Transgenic mice with an inhibin alpha subunit gene deletion develop stromal/granulosa cell tumours suggesting that the alpha subunit is a tumour suppressor gene. The role of inhibin and activin is reviewed in ovarian cancer both as a measure of proven clinical utility in diagnosis and management and also as a factor in the pathogenesis of these tumours. In order to place these findings into perspective the biology of inhibin/activin and of other members of the TGFbeta superfamily is also discussed.

scholarly journals TGFβ signaling regulates epithelial–mesenchymal plasticity in ovarian cancer ascites-derived spheroids

2015 ◽  
Vol 23 (3) ◽  
pp. 147-159 ◽  
Author(s):  
Samah Rafehi ◽  
Yudith Ramos Valdes ◽  
Monique Bertrand ◽  
Jacob McGee ◽  
Michel Préfontaine ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Type I ◽  
Tgfβ Signaling ◽  
Mesenchymal Transition ◽  
Tumor Cell Migration ◽  
Cancer Pathogenesis

Epithelial–mesenchymal transition (EMT) serves as a key mechanism driving tumor cell migration, invasion, and metastasis in many carcinomas. Transforming growth factor-beta (TGFβ) signaling is implicated in several steps during cancer pathogenesis and acts as a classical inducer of EMT. Since epithelial ovarian cancer (EOC) cells have the potential to switch between epithelial and mesenchymal states during metastasis, we predicted that modulation of TGFβ signaling would significantly impact EMT and the malignant potential of EOC spheroid cells. Ovarian cancer patient ascites-derived cells naturally underwent an EMT response when aggregating into spheroids, and this was reversed upon spheroid re-attachment to a substratum. CDH1/E-cadherin expression was markedly reduced in spheroids compared with adherent cells, in concert with an up-regulation of several transcriptional repressors, i.e., SNAI1/Snail, TWIST1/2, and ZEB2. Treatment of EOC spheroids with the TGFβ type I receptor inhibitor, SB-431542, potently blocked the endogenous activation of EMT in spheroids. Furthermore, treatment of spheroids with SB-431542 upon re-attachment enhanced the epithelial phenotype of dispersing cells and significantly decreased cell motility and Transwell migration. Spheroid formation was significantly compromised by exposure to SB-431542 that correlated with a reduction in cell viability particularly in combination with carboplatin treatment. Thus, our findings are the first to demonstrate that intact TGFβ signaling is required to control EMT in EOC ascites-derived cell spheroids, and it promotes the malignant characteristics of these structures. As such, we show the therapeutic potential for targeted inhibition of this pathway in ovarian cancer patients with late-stage disease.

scholarly journals The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases

2021 ◽  
Author(s):  
Ielizaveta Gorodetska ◽  
Anna Offermann ◽  
Jakob Pueschel ◽  
Vasyl Lukiyanchuk ◽  
Diana Gaete ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Development ◽  
Therapy Resistance ◽  
Radiation Sensitivity ◽  
Strand Break ◽  
Mesenchymal Transition

Cancer stem cells (CSC) are characterized by high self-renewal capacity, tumor-initiating potential, and therapy resistance. Aldehyde dehydrogenase (ALDH)+ cell population serves as an indicator of prostate CSCs with increased therapy resistance, enhanced DNA double-strand break repair, and activated epithelial-mesenchymal transition (EMT) and migration. Numerous ALDH genes contribute to ALDH enzymatic activity; however, only some of them showed clinical relevance. We found that ALDH1A1 and ALDH1A3 genes functionally regulate CSC properties and radiation sensitivity of PCa. We revealed a negative correlation between ALDH1A1 and ALDH1A3 expression in publicly available prostate cancer (PCa) datasets and demonstrated that ALDH1A1 and ALDH1A3 have opposing predictive value for biochemical recurrence-free survival. Our data suggest an association of ALDH1A1 with the metastatic burden, elucidating the role of ALDH genes in the metastatic spread and homing to the bone, which can be, at least partially, attributed to regulating the transforming growth factor beta 1 (TGFB1) and matrix metalloproteinases (MMPs). ALDH genes play a diverse role in PCa development under AR and β-catenin-dependent regulation, with ALDH1A1 becoming dominant in later stages of tumor development when PCa cells gain androgen independence. Taken together, our results indicate that ALDH1A1 and ALDH1A3 modulate PCa radiosensitivity, regulate CSCs phenotype, and spread of PCa cells to the bone, therefore having clinical implication for identifying patients at high risk for progression to metastatic disease.

scholarly journals Role of the Adjacent Stroma Cells in Prostate Cancer Development and Progression: Synergy between TGF-βand IGF Signaling

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Chung Lee ◽  
Zhenyu Jia ◽  
Farah Rahmatpanah ◽  
Qiang Zhang ◽  
Xiaolin Zi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cancer Progression ◽  
Transforming Growth Factor Beta ◽  
Stromal Cells ◽  
Transforming Growth Factor ◽  
Reciprocal Relationship ◽  
Cancer Development ◽  
Igf Signaling

This review postulates the role of transforming growth factor-beta (TGF-β) and insulin-like growth factor (IGF-I/IGF-II) signaling in stromal cells during prostate carcinogenesis and progression. It is known that stromal cells have a reciprocal relationship to the adjacent epithelial cells in the maintenance of structural and functional integrity of the prostate. An interaction between TGF-βand IGF signaling occupies a central part in this stromal-epithelial interaction. An increase in TGF-βand IGF signaling will set off the imbalance of this relationship and will lead to cancer development. A continuous input from TGF-βand IGF in the tumor microenvironment will result in cancer progression. Understanding of these events can help prevention, diagnosis, and therapy of prostate cancer.

scholarly journals Role of endocannabinoid CB1 receptors in Streptozotocin-induced uninephrectomised Wistar rats in diabetic nephropathy

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jayarami Reddy Medapati ◽  
Deepthi Rapaka ◽  
Veera Raghavulu Bitra ◽  
Santhosh Kumar Ranajit ◽  
Girija Sankar Guntuku ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Morphological Changes ◽  
Serum Levels ◽  
Cb1 Receptors ◽  
Protective Effects ◽  
Renal Hypertrophy ◽  
Necrosis Factor Alpha

Abstract Background The endocannabinoid CB1 receptor is known to have protective effects in kidney disease. The aim of the present study is to evaluate the potential agonistic and antagonistic actions and to determine the renoprotective potential of CB1 receptors in diabetic nephropathy. The present work investigates the possible role of CB1 receptors in the pathogenesis of diabetes-induced nephropathy. Streptozotocin (STZ) (55 mg/kg, i.p., once) is administered to uninephrectomised rats for induction of experimental diabetes mellitus. The CB1 agonist (oleamide) and CB1 antagonist (AM6545) treatment were initiated in diabetic rats after 1 week of STZ administration and were given for 24 weeks. Results The progress in diabetic nephropathy is estimated biochemically by measuring serum creatinine (1.28±0.03) (p < 0.005), blood urea nitrogen (67.6± 2.10) (p < 0.001), urinary microprotein (74.62± 3.47) (p < 0.005) and urinary albuminuria (28.31±1.17) (p < 0.0001). Renal inflammation was assessed by estimating serum levels of tumor necrosis factor alpha (75.69±1.51) (p < 0.001) and transforming growth factor beta (8.73±0.31) (p < 0.001). Renal morphological changes were assessed by estimating renal hypertrophy (7.38± 0.26) (p < 0.005) and renal collagen content (10.42± 0.48) (p < 0.001). Conclusions From the above findings, it can be said that diabetes-induced nephropathy may be associated with overexpression of CB1 receptors and blockade of CB1 receptors might be beneficial in ameliorating the diabetes-induced nephropathy. Graphical abstract

scholarly journals Diagnostic Role of 18F-PSMA-1007 PET/CT in Prostate Cancer Staging: A Systematic Review

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 552
Author(s):  
Salam Awenat ◽  
Arnoldo Piccardo ◽  
Patricia Carvoeiras ◽  
Giovanni Signore ◽  
Luca Giovanella ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Diagnostic Accuracy ◽  
Metastatic Disease ◽  
Cancer Staging ◽  
Relevant Information ◽  
Cochrane Library ◽  
Number Of Patients ◽  
Pet Ct

Background: The use of prostate-specific membrane antigen (PSMA)-targeted agents for staging prostate cancer (PCa) patients using positron emission tomography/computed tomography (PET/CT) is increasing worldwide. We performed a systematic review on the role of 18F-PSMA-1007 PET/CT in PCa staging to provide evidence-based data in this setting. Methods: A comprehensive computer literature search of PubMed/MEDLINE and Cochrane Library databases for studies using 18F-PSMA-1007 PET/CT in PCa staging was performed until 31 December 2020. Eligible articles were selected and relevant information was extracted from the original articles by two authors independently. Results: Eight articles (369 patients) evaluating the role of 18F-PSMA-1007 PET/CT in PCa staging were selected. These studies were quite heterogeneous, but, overall, they demonstrated a good diagnostic accuracy of 18F-PSMA-1007 PET/CT in detecting PCa lesions at staging. Overall, higher primary PCa aggressiveness was associated with higher 18F-PSMA-1007 uptake. When compared with other radiological and scintigraphic imaging methods, 18F-PSMA-1007 PET/CT had superior sensitivity in detecting metastatic disease and the highest inter-reader agreement. 18F-PSMA-1007 PET/CT showed similar results in terms of diagnostic accuracy for PCa staging compared with PET/CT with other PSMA-targeted tracers. Dual imaging with multi-parametric magnetic resonance imaging and 18F-PSMA-1007 PET/CT may improve staging of primary PCa. Notably, 18F-PSMA-1007-PET/CT may detect metastatic disease in a significant number of patients with negative standard imaging. Conclusions: 18F-PSMA-1007 PET/CT demonstrated a good accuracy in PCa staging, with similar results compared with other PSMA-targeted radiopharmaceuticals. This method could substitute bone scintigraphy and conventional abdominal imaging for PCa staging. Prospective multicentric studies are needed to confirm these findings.

Expression of transforming growth factor-beta 1 in prostate cancer.

Endocrinology ◽  
1994 ◽  
Vol 135 (5) ◽  
pp. 2240-2247 ◽  
Author(s):  
M S Steiner ◽  
Z Z Zhou ◽  
D C Tonb ◽  
E R Barrack
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta
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