Background: In recent decades, obesity has widely emerged as an important risk factor for prostate cancer (PCa). Adipose tissue and PCa cells have been shown to orchestrate a complex interaction network to support tumor growth and evolution; nonetheless, the study of this communication has only been focused on soluble factors, although increasing evidence highlights the key role of extracellular vesicles (EVs) in the modulation of tumor progression. Methods and Results: In the present study, we found that EVs derived from 3T3-L1 adipocytes could affect PC3 and DU145 PCa cell traits, inducing increased proliferation, migration and invasion. Furthermore, conditioning of both PCa cell lines with adipocyte-released EVs resulted in lower sensitivity to docetaxel, with reduced phosphatidylserine externalization and decreased caspase 3 and PARP cleavage. In particular, these alterations were paralleled by an Akt/HIF-1 ff axis-related Warburg effect, characterized by enhanced glucose consumption, lactate release and ATP production. Conclusions: Collectively, these findings demonstrate that EV-mediated crosstalk exists between adipocytes and PCa, driving tumor aggressiveness.

Adipocyte-Derived Extracellular Vesicles Promote Prostate Cancer Cell Aggressiveness by Enabling Multiple Phenotypic and Metabolic Changes / F. Fontana, M. Anselmi, E. Carollo, P. Sartori, P. Procacci, D. Carter, P. Limonta. - In: CELLS. - ISSN 2073-4409. - 11:15(2022 Aug 03), pp. 2388.1-2388.11. [10.3390/cells11152388]

Adipocyte-Derived Extracellular Vesicles Promote Prostate Cancer Cell Aggressiveness by Enabling Multiple Phenotypic and Metabolic Changes

F. Fontana
Primo
;
M. Anselmi;P. Sartori;P. Procacci;P. Limonta
2022

Abstract

Background: In recent decades, obesity has widely emerged as an important risk factor for prostate cancer (PCa). Adipose tissue and PCa cells have been shown to orchestrate a complex interaction network to support tumor growth and evolution; nonetheless, the study of this communication has only been focused on soluble factors, although increasing evidence highlights the key role of extracellular vesicles (EVs) in the modulation of tumor progression. Methods and Results: In the present study, we found that EVs derived from 3T3-L1 adipocytes could affect PC3 and DU145 PCa cell traits, inducing increased proliferation, migration and invasion. Furthermore, conditioning of both PCa cell lines with adipocyte-released EVs resulted in lower sensitivity to docetaxel, with reduced phosphatidylserine externalization and decreased caspase 3 and PARP cleavage. In particular, these alterations were paralleled by an Akt/HIF-1 ff axis-related Warburg effect, characterized by enhanced glucose consumption, lactate release and ATP production. Conclusions: Collectively, these findings demonstrate that EV-mediated crosstalk exists between adipocytes and PCa, driving tumor aggressiveness.
Warburg effect; adipocytes; chemoresistance; extracellular vesicles; metastasis; obesity; prostate cancer; 3T3-L1 Cells; Adipocytes; Animals; Humans; Male; Mice; Extracellular Vesicles; Prostatic Neoplasms
Settore BIO/13 - Biologia Applicata
PRIN201517PLIMO - Useful experimental models for dissecting the molecular links between cancer development/progression and the obesity epidemic - LIMONTA, PATRIZIA - PRIN2015 - PRIN bando 2015 - 2017
DECC18ACORS_01 - Dipartimenti di Eccellenza 2018-2022 - Dipartimento di SCIENZE FARMACOLOGICHE E BIOMOLECOLARI - CORSINI, ALBERTO - DECC - Bando Dipartimenti di Eccellenza - 2018
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/939269
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