ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy
Antiandrogen therapies are effectively used to treat advanced prostate cancer, but eventually cancer adaptation drives unresolved metastatic castration-resistant prostate cancer (mCRPC). Adipose tissue influences metabolic reprogramming in cancer and was proposed as a contributor to therapy resistan...
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| Language: | English |
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Elsevier
2025-02-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S259000642400485X |
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| author | Agathe Bessot Joan Röhl Maria Emmerich Anton Klotz Akhilandeshwari Ravichandran Christoph Meinert David Waugh Jacqui McGovern Jenni Gunter Nathalie Bock |
| author_facet | Agathe Bessot Joan Röhl Maria Emmerich Anton Klotz Akhilandeshwari Ravichandran Christoph Meinert David Waugh Jacqui McGovern Jenni Gunter Nathalie Bock |
| author_sort | Agathe Bessot |
| collection | DOAJ |
| description | Antiandrogen therapies are effectively used to treat advanced prostate cancer, but eventually cancer adaptation drives unresolved metastatic castration-resistant prostate cancer (mCRPC). Adipose tissue influences metabolic reprogramming in cancer and was proposed as a contributor to therapy resistance. Using extracellular matrix (ECM)-mimicking hydrogel coculture models of human adipocytes and prostate cancer cells, we show that adipocytes from subcutaneous or bone marrow fat have dissimilar responses under the antiandrogen Enzalutamide. We demonstrate that androgen receptor (AR)-dependent cancer cells (LNCaP) are more influenced by human adipocytes than AR-independent cells (C4-2B), with altered lipid metabolism and adipokine secretion. This response changes under Enzalutamide, with increased AR expression and adipogenic and lipogenic genes in cancer cells and decreased lipid content and gene dysregulation associated with insulin resistance in adipocytes. This is in line with the metabolic syndrome that men with mCRPC under Enzalutamide experience. The all-human, all-3D, models presented here provide a significant advance to dissect the role of fat in therapy response for mCRPC. |
| format | Article |
| id | doaj-art-352dd607a1fb4397abbd7bea0778df74 |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-352dd607a1fb4397abbd7bea0778df742025-01-17T04:52:10ZengElsevierMaterials Today Bio2590-00642025-02-0130101424ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapyAgathe Bessot0Joan Röhl1Maria Emmerich2Anton Klotz3Akhilandeshwari Ravichandran4Christoph Meinert5David Waugh6Jacqui McGovern7Jenni Gunter8Nathalie Bock9School of Biomedical Sciences, Faculty of Health, and Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, QLD, 4102, Australia; Centre for Biomedical Technologies, QUT, Brisbane, QLD, 4000, Australia; Max Planck Queensland Centre, Brisbane, QLD, 4000, Australia; Australian Prostate Cancer Research Centre (APCRC-Q), QUT, Brisbane, QLD, 4102, AustraliaFaculty of Health Sciences and Medicine, Bond University, Robina, QLD, 4226, AustraliaSchool of Computation, Information and Technology, Technical University of Munich (TUM), Munich, GermanyDivision of Gastroenterology and Hepatology, Department of Internal Medicine 3, Medical University of Vienna, Vienna, AustriaCentre for Biomedical Technologies, QUT, Brisbane, QLD, 4000, Australia; School of Mechanical, Medical and Process Engineering, Faculty of Engineering, QUT, Brisbane, QLD 4000, Australia; Australian Research Council (ARC) Training Centre for Cell and Tissue Engineering Technologies (CTET), QUT, Brisbane, QLD 4000, AustraliaGelomics Pty Ltd., Brisbane, QLD 4059, AustraliaCentre for Cancer Biology, University of South Australia, Adelaide, SA 5005, AustraliaSchool of Biomedical Sciences, Faculty of Health, and Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, QLD, 4102, Australia; Centre for Biomedical Technologies, QUT, Brisbane, QLD, 4000, Australia; Max Planck Queensland Centre, Brisbane, QLD, 4000, Australia; Australian Research Council (ARC) Training Centre for Cell and Tissue Engineering Technologies (CTET), QUT, Brisbane, QLD 4000, AustraliaSchool of Biomedical Sciences, Faculty of Health, and Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, QLD, 4102, Australia; Australian Prostate Cancer Research Centre (APCRC-Q), QUT, Brisbane, QLD, 4102, AustraliaSchool of Biomedical Sciences, Faculty of Health, and Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, QLD, 4102, Australia; Centre for Biomedical Technologies, QUT, Brisbane, QLD, 4000, Australia; Max Planck Queensland Centre, Brisbane, QLD, 4000, Australia; Australian Prostate Cancer Research Centre (APCRC-Q), QUT, Brisbane, QLD, 4102, Australia; Australian Research Council (ARC) Training Centre for Multiscale 3D Imaging, Modelling, and Manufacturing (M3D Innovation), Queensland University of Technology, Brisbane, QLD 4000, Australia; Corresponding author. Translational Research Institute, Queensland University of Technology, 37 Kent Street, Woolloongabba 4102, QLD, Australia.Antiandrogen therapies are effectively used to treat advanced prostate cancer, but eventually cancer adaptation drives unresolved metastatic castration-resistant prostate cancer (mCRPC). Adipose tissue influences metabolic reprogramming in cancer and was proposed as a contributor to therapy resistance. Using extracellular matrix (ECM)-mimicking hydrogel coculture models of human adipocytes and prostate cancer cells, we show that adipocytes from subcutaneous or bone marrow fat have dissimilar responses under the antiandrogen Enzalutamide. We demonstrate that androgen receptor (AR)-dependent cancer cells (LNCaP) are more influenced by human adipocytes than AR-independent cells (C4-2B), with altered lipid metabolism and adipokine secretion. This response changes under Enzalutamide, with increased AR expression and adipogenic and lipogenic genes in cancer cells and decreased lipid content and gene dysregulation associated with insulin resistance in adipocytes. This is in line with the metabolic syndrome that men with mCRPC under Enzalutamide experience. The all-human, all-3D, models presented here provide a significant advance to dissect the role of fat in therapy response for mCRPC.http://www.sciencedirect.com/science/article/pii/S259000642400485XAdipose modelsSGBS cellsBone marrow adipocytesProstate cancerAndrogen receptorEnzalutamide |
| spellingShingle | Agathe Bessot Joan Röhl Maria Emmerich Anton Klotz Akhilandeshwari Ravichandran Christoph Meinert David Waugh Jacqui McGovern Jenni Gunter Nathalie Bock ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy Materials Today Bio Adipose models SGBS cells Bone marrow adipocytes Prostate cancer Androgen receptor Enzalutamide |
| title | ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy |
| title_full | ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy |
| title_fullStr | ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy |
| title_full_unstemmed | ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy |
| title_short | ECM-mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer-adipocyte crosstalk under antiandrogen therapy |
| title_sort | ecm mimicking hydrogel models of human adipose tissue identify deregulated lipid metabolism in the prostate cancer adipocyte crosstalk under antiandrogen therapy |
| topic | Adipose models SGBS cells Bone marrow adipocytes Prostate cancer Androgen receptor Enzalutamide |
| url | http://www.sciencedirect.com/science/article/pii/S259000642400485X |
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