Estrogen receptors in urogenital schistosomiasis and bladder cancer: Estrogen receptor alpha-mediated cell proliferation.

Published on Jun 2, 2020in Urologic Oncology-seminars and Original Investigations2.882
· DOI :10.1016/J.UROLONC.2020.04.022
Carina Bernardo5
Estimated H-index: 5
(University of Aveiro),
Júlio Gonçalves dos Santos1
Estimated H-index: 1
(University of Porto)
+ 11 AuthorsLúcio Lara Santos29
Estimated H-index: 29
Sources
Abstract
Abstract Estrogen-like metabolites have been identified in S. haematobium, the helminth parasite that causes urogenital schistosomiasis (UGS) and in patients´ blood and urine during UGS. Estrogen receptor (ER) activation is enriched in the luminal molecular subtype bladder cancer (BlaCa). To date, the significance of ER to these diseases remains elusive. We evaluated ERα and ERβ expression in UGS-related BlaCa (n = 27), UGS-related non-malignant lesions (n = 35), and noninfected BlaCa (n = 80). We investigated the potential of ERα to recognize S. haematobium-derived metabolites by docking and molecular dynamics simulations and studied ERα modulation in vitro using 3 BlaCa cell lines, T24, 5637 and HT1376. ERα was expressed in tumor and stromal cells in approximately 20% noninfected cases and in 30% of UGS-related BlaCa, predominantly in the epithelial cells. Overall, ERα expression was associated with features of tumor aggressiveness such as high proliferation and p53 positive expression. ERα expression correlated with presence of schistosome eggs. ERβ was widely expressed in both cohorts but weaker in UGS-related cases. molecular dynamics simulations of the 4 most abundant S. haematobium-derived metabolites revealed that smaller metabolites have comparable affinity for the ERα active state than 17β-estradiol, while the larger metabolites present higher affinity. Our in vitro findings suggested that ERα activation promotes proliferation in ERα expressing BlaCa cells and that this can be reverted with anti-estrogenic therapy. In summary, we report differential ER expression between UGS-related BlaCa and noninfected BlaCa and provide evidence supporting a role of active ERα during UGS and UGS-induced carcinogenesis.
📖 Papers frequently viewed together
6 Authors (Na Wei, ..., Hextan Y.S. Ngan)
299 Citations
3 Authors (Liren Ding, ..., Z.G. Wang)
2 Citations
References66
Newest
#1Aurélie KamounH-Index: 3
Last. John N. Weinstein (University of Texas MD Anderson Cancer Center)H-Index: 112
view all 42 authors...
Abstract Background Muscle-invasive bladder cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, but the diversity of their subtype sets impedes their clinical application. Objective To achieve an international consensus on MIBC molecular subtypes that reconciles the published classification schemes. Design, setting, and participants We used 1750 MIBC transcriptomic profiles from 16 published datasets and two a...
152 CitationsSource
#1Gottfrid Sjödahl (Lund University)H-Index: 20
#2Chelsea L. Jackson (Queen's University)H-Index: 2
Last. David M. Berman (Queen's University)H-Index: 44
view all 5 authors...
Bladder cancers are biologically and clinically heterogeneous. Recent large-scale transcriptomic profiling studies focusing on life-threatening muscle-invasive cases have demonstrated a small number of molecularly distinct clusters that largely explain their heterogeneity. Similar to breast cancer, these clusters reflect intrinsic urothelial cell-type differentiation programs, including those with luminal and basal cell characteristics. Also like breast cancer, each cell-based subtype demonstrat...
29 CitationsSource
#1Matic Pavlin (SISSA: International School for Advanced Studies)H-Index: 7
#2Angelo Spinello (SISSA: International School for Advanced Studies)H-Index: 15
Last. Alessandra Magistrato (SISSA: International School for Advanced Studies)H-Index: 26
view all 8 authors...
Somatic mutations of the Estrogen Receptor α (ERα) occur with an up to 40% incidence in ER sensitive breast cancer (BC) patients undergoing prolonged endocrine treatments. These polymorphisms are implicated in acquired resistance, disease relapse, and increased mortality rates, hence representing a current major clinical challenge. Here, multi-microseconds (12.5 µs) molecular dynamics simulations revealed that recurrent ERα polymorphisms (i. e. L536Q, Y537S, Y537N, D538G) (mERα) are constitutive...
28 CitationsSource
#2Campbell Grant (WashU: Washington University in St. Louis)H-Index: 1
Last. Piyush K. AgarwalH-Index: 25
view all 4 authors...
Abstract Background The treatment options for non–muscle invasive bladder cancer (NMIBC) remain limited. Bacillus Calmette-Guerin (BCG) was the last major breakthrough in bladder cancer therapy almost 4 decades ago. There have been improvements in the understanding of immune therapies and cancer biology, leading to the development of novel agents. This has led to many clinical trials that are currently underway to find the next generation of therapies for NMIBC. Method We reviewed clinicaltrials...
13 CitationsSource
#1Paul J. Brindley (GW: George Washington University)H-Index: 57
#2Alex Loukas (Australian Institute of Tropical Health and Medicine)H-Index: 70
Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Gro...
32 CitationsSource
#1Sandra Andersson (Science for Life Laboratory)H-Index: 26
#2Mårten Sundberg (Science for Life Laboratory)H-Index: 3
Last. Anna Asplund (Science for Life Laboratory)H-Index: 15
view all 12 authors...
A large body of work into the role of oestrogen receptor b (ERb) in breast cancer is contradictory, hindering future progress. Here the authors conduct extensive validation of anti-ERb antibodies , and show that normal and cancerous breast tissue do not express ERb, consistent with RNA-seq data.
95 CitationsSource
#1Chengjian Mao (UIUC: University of Illinois at Urbana–Champaign)H-Index: 12
#2Mara Livezey (UIUC: University of Illinois at Urbana–Champaign)H-Index: 6
Last. David J. Shapiro (UIUC: University of Illinois at Urbana–Champaign)H-Index: 42
view all 4 authors...
Antiestrogen Resistant Cell Lines Expressing Estrogen Receptor α Mutations Upregulate the Unfolded Protein Response and are Killed by BHPI
29 CitationsSource
#1Colin R. Groom (University of Cambridge)H-Index: 24
#2Ian J. Bruno (University of Cambridge)H-Index: 14
Last. Suzanna C. Ward (University of Cambridge)H-Index: 4
view all 4 authors...
The Cambridge Structural Database (CSD) contains a complete record of all published organic and metal–organic small-molecule crystal structures. The database has been in operation for over 50 years and continues to be the primary means of sharing structural chemistry data and knowledge across disciplines. As well as structures that are made public to support scientific articles, it includes many structures published directly as CSD Communications. All structures are processed both computationall...
3,608 CitationsSource
#1Paul J. Brindley (GW: George Washington University)H-Index: 57
#2José Manuel Correia da Costa (University of Porto)H-Index: 22
Last. Banchob Sripa (KKU: Khon Kaen University)H-Index: 49
view all 3 authors...
Infections with Opisthorchis viverrini , Clonorchis sinensis , and Schistosoma haematobium are classified as group 1 biological carcinogens: definitive causes of cancer. These worms are metazoan eukaryotes, unlike the other group 1 carcinogens including human papilloma virus, hepatitis C virus, and Helicobacter pylori . By contrast, infections with phylogenetic relatives of these helminths, also trematodes of the phylum Platyhelminthes and major human pathogens, are not carcinogenic. These incon...
60 CitationsSource
#1Winston Tan (Mayo Clinic)H-Index: 24
#2Stephen A. Boorjian (Mayo Clinic)H-Index: 62
Last. Bradley C. Leibovich (Mayo Clinic)H-Index: 72
view all 8 authors...
Abstract Objective Bladder cancer has the sixth highest incidence in the United States. Treatment of metastatic bladder cancer is difficult, and mortality is certain. There are certain pathways in cancer growth and progression that are important in bladder cancer development. Recently, the estrogen pathway has been found to be a potential target for therapy. Methods We identified 410 patients treated with radical cystectomy for urothelial cell carcinoma between 1990 and 1994. We obtained represe...
14 CitationsSource
Cited By3
Newest
#1Ève Pellerin (Laval University)H-Index: 3
#2Christophe Caneparo (Laval University)H-Index: 1
Last. Martin Pelletier (Laval University)H-Index: 25
view all 5 authors...
Source
Source
#1Takuro Goto (URMC: University of Rochester Medical Center)H-Index: 3
#2Hiroshi Miyamoto (URMC: University of Rochester Medical Center)H-Index: 46
Epidemiological data have indicated that there are some sex-related differences in bladder cancer. Indeed, the incidence of bladder cancer in men has been substantially higher than that in women throughout the world, while women tend to have higher stage disease and poorer prognosis. These gender disparities have prompted to investigate sex hormones and their cognitive receptors in bladder cancer. Specifically, estrogen receptors, including estrogen receptor-α and estrogen receptor-β, have been ...
Source