The protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor-antagonists and -agonist to stimulate growth of target cells
Abstract Background Prostate cancer (PCa) is a prevalent malignancy in men worldwide, ranking as the second leading cause of cancer-related death in Western countries. Various PCa hormone therapies, such as androgen receptor (AR)-antagonists or supraphysiological androgen level (SAL) reduce cancer c...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-04-01
|
| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-024-01584-z |
| _version_ | 1797209239895146496 |
|---|---|
| author | Golnaz Atri Roozbahani Miriam Kokal-Ribaudo Mehdi Heidari Horestani Thanakorn Pungsrinont Aria Baniahmad |
| author_facet | Golnaz Atri Roozbahani Miriam Kokal-Ribaudo Mehdi Heidari Horestani Thanakorn Pungsrinont Aria Baniahmad |
| author_sort | Golnaz Atri Roozbahani |
| collection | DOAJ |
| description | Abstract Background Prostate cancer (PCa) is a prevalent malignancy in men worldwide, ranking as the second leading cause of cancer-related death in Western countries. Various PCa hormone therapies, such as androgen receptor (AR)-antagonists or supraphysiological androgen level (SAL) reduce cancer cell proliferation. However, treated cells may influence the growth of neighboring cells through secreted exosomes in the tumor microenvironment (TME). Here, the change of protein content of exosomes secreted from PCa cells through treatment with different AR-antagonists or SAL has been analyzed. Methods Isolation of exosomes via ultracentrifugation of treated human PCa LNCaP cells with AR-agonist and various AR-antagonists; analysis of cellular senescence by detection of senescence associated beta galactosidase activity (SA β-Gal); Western blotting and immunofluorescence staining; Mass spectrometry (MS-spec) of exosomes and bioinformatic analyses to identify ligand-specific exosomal proteins. Growth assays to analyze influence of exosomes on non-treated cells. Results MS-spec analysis identified ligand-specific proteins in exosomes. One thousand seventy proteins were up- and 52 proteins downregulated by SAL whereas enzalutamide upregulated 151 proteins and downregulated 42 exosomal proteins. The bioinformatic prediction indicates an up-regulation of pro-proliferative pathways. AR ligands augment hub factors in exosomes that include AKT1, CALM1, PAK2 and CTNND1. Accordingly, functional assays confirmed that the isolated exosomes from AR-ligand treated cells promote growth of untreated PCa cells. Conclusion The data suggest that the cargo of exosomes is controlled by AR-agonist and -antagonists and distinct among the AR-antagonists. Further, exosomes promote growth that might influence the TME. This finding sheds light into the complex interplay between AR signaling and exosome-mediated communication between PCa cells. |
| first_indexed | 2024-04-24T09:51:33Z |
| format | Article |
| id | doaj.art-de96ed5ad5e045bba9b11e537ca25710 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-24T09:51:33Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-de96ed5ad5e045bba9b11e537ca257102024-04-14T11:23:12ZengBMCCell Communication and Signaling1478-811X2024-04-0122111710.1186/s12964-024-01584-zThe protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor-antagonists and -agonist to stimulate growth of target cellsGolnaz Atri Roozbahani0Miriam Kokal-Ribaudo1Mehdi Heidari Horestani2Thanakorn Pungsrinont3Aria Baniahmad4Institute of Human Genetics, Jena University HospitalInstitute of Human Genetics, Jena University HospitalInstitute of Human Genetics, Jena University HospitalInstitute of Human Genetics, Jena University HospitalInstitute of Human Genetics, Jena University HospitalAbstract Background Prostate cancer (PCa) is a prevalent malignancy in men worldwide, ranking as the second leading cause of cancer-related death in Western countries. Various PCa hormone therapies, such as androgen receptor (AR)-antagonists or supraphysiological androgen level (SAL) reduce cancer cell proliferation. However, treated cells may influence the growth of neighboring cells through secreted exosomes in the tumor microenvironment (TME). Here, the change of protein content of exosomes secreted from PCa cells through treatment with different AR-antagonists or SAL has been analyzed. Methods Isolation of exosomes via ultracentrifugation of treated human PCa LNCaP cells with AR-agonist and various AR-antagonists; analysis of cellular senescence by detection of senescence associated beta galactosidase activity (SA β-Gal); Western blotting and immunofluorescence staining; Mass spectrometry (MS-spec) of exosomes and bioinformatic analyses to identify ligand-specific exosomal proteins. Growth assays to analyze influence of exosomes on non-treated cells. Results MS-spec analysis identified ligand-specific proteins in exosomes. One thousand seventy proteins were up- and 52 proteins downregulated by SAL whereas enzalutamide upregulated 151 proteins and downregulated 42 exosomal proteins. The bioinformatic prediction indicates an up-regulation of pro-proliferative pathways. AR ligands augment hub factors in exosomes that include AKT1, CALM1, PAK2 and CTNND1. Accordingly, functional assays confirmed that the isolated exosomes from AR-ligand treated cells promote growth of untreated PCa cells. Conclusion The data suggest that the cargo of exosomes is controlled by AR-agonist and -antagonists and distinct among the AR-antagonists. Further, exosomes promote growth that might influence the TME. This finding sheds light into the complex interplay between AR signaling and exosome-mediated communication between PCa cells.https://doi.org/10.1186/s12964-024-01584-zProstate cancerAndrogen receptor agonistAntagonistCellular senescenceSupraphysiological androgen levelsExtracellular vesicles |
| spellingShingle | Golnaz Atri Roozbahani Miriam Kokal-Ribaudo Mehdi Heidari Horestani Thanakorn Pungsrinont Aria Baniahmad The protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor-antagonists and -agonist to stimulate growth of target cells Cell Communication and Signaling Prostate cancer Androgen receptor agonist Antagonist Cellular senescence Supraphysiological androgen levels Extracellular vesicles |
| title | The protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor-antagonists and -agonist to stimulate growth of target cells |
| title_full | The protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor-antagonists and -agonist to stimulate growth of target cells |
| title_fullStr | The protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor-antagonists and -agonist to stimulate growth of target cells |
| title_full_unstemmed | The protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor-antagonists and -agonist to stimulate growth of target cells |
| title_short | The protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor-antagonists and -agonist to stimulate growth of target cells |
| title_sort | protein composition of exosomes released by prostate cancer cells is distinctly regulated by androgen receptor antagonists and agonist to stimulate growth of target cells |
| topic | Prostate cancer Androgen receptor agonist Antagonist Cellular senescence Supraphysiological androgen levels Extracellular vesicles |
| url | https://doi.org/10.1186/s12964-024-01584-z |
| work_keys_str_mv | AT golnazatriroozbahani theproteincompositionofexosomesreleasedbyprostatecancercellsisdistinctlyregulatedbyandrogenreceptorantagonistsandagonisttostimulategrowthoftargetcells AT miriamkokalribaudo theproteincompositionofexosomesreleasedbyprostatecancercellsisdistinctlyregulatedbyandrogenreceptorantagonistsandagonisttostimulategrowthoftargetcells AT mehdiheidarihorestani theproteincompositionofexosomesreleasedbyprostatecancercellsisdistinctlyregulatedbyandrogenreceptorantagonistsandagonisttostimulategrowthoftargetcells AT thanakornpungsrinont theproteincompositionofexosomesreleasedbyprostatecancercellsisdistinctlyregulatedbyandrogenreceptorantagonistsandagonisttostimulategrowthoftargetcells AT ariabaniahmad theproteincompositionofexosomesreleasedbyprostatecancercellsisdistinctlyregulatedbyandrogenreceptorantagonistsandagonisttostimulategrowthoftargetcells AT golnazatriroozbahani proteincompositionofexosomesreleasedbyprostatecancercellsisdistinctlyregulatedbyandrogenreceptorantagonistsandagonisttostimulategrowthoftargetcells AT miriamkokalribaudo proteincompositionofexosomesreleasedbyprostatecancercellsisdistinctlyregulatedbyandrogenreceptorantagonistsandagonisttostimulategrowthoftargetcells AT mehdiheidarihorestani proteincompositionofexosomesreleasedbyprostatecancercellsisdistinctlyregulatedbyandrogenreceptorantagonistsandagonisttostimulategrowthoftargetcells AT thanakornpungsrinont proteincompositionofexosomesreleasedbyprostatecancercellsisdistinctlyregulatedbyandrogenreceptorantagonistsandagonisttostimulategrowthoftargetcells AT ariabaniahmad proteincompositionofexosomesreleasedbyprostatecancercellsisdistinctlyregulatedbyandrogenreceptorantagonistsandagonisttostimulategrowthoftargetcells |