Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia.
Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-12-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3000948 |
| _version_ | 1819142164137902080 |
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| author | Laura Bousset Amandine Septier Julio Bunay Allison Voisin Rachel Guiton Christelle Damon-Soubeyrant Yoan Renaud Angélique De Haze Vincent Sapin Anne Fogli Amandine Rambur Cyrille De Joussineau Ayhan Kocer Amalia Trousson Joëlle Henry-Berger Marcus Höring Gerhard Liebisch Silke Matysik Jean-Marc A Lobaccaro Laurent Morel Silvère Baron |
| author_facet | Laura Bousset Amandine Septier Julio Bunay Allison Voisin Rachel Guiton Christelle Damon-Soubeyrant Yoan Renaud Angélique De Haze Vincent Sapin Anne Fogli Amandine Rambur Cyrille De Joussineau Ayhan Kocer Amalia Trousson Joëlle Henry-Berger Marcus Höring Gerhard Liebisch Silke Matysik Jean-Marc A Lobaccaro Laurent Morel Silvère Baron |
| author_sort | Laura Bousset |
| collection | DOAJ |
| description | Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders. |
| first_indexed | 2024-12-22T12:05:59Z |
| format | Article |
| id | doaj.art-05cca25ebd094bacb880db359ab83169 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-22T12:05:59Z |
| publishDate | 2020-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-05cca25ebd094bacb880db359ab831692022-12-21T18:26:25ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852020-12-011812e300094810.1371/journal.pbio.3000948Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia.Laura BoussetAmandine SeptierJulio BunayAllison VoisinRachel GuitonChristelle Damon-SoubeyrantYoan RenaudAngélique De HazeVincent SapinAnne FogliAmandine RamburCyrille De JoussineauAyhan KocerAmalia TroussonJoëlle Henry-BergerMarcus HöringGerhard LiebischSilke MatysikJean-Marc A LobaccaroLaurent MorelSilvère BaronChronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders.https://doi.org/10.1371/journal.pbio.3000948 |
| spellingShingle | Laura Bousset Amandine Septier Julio Bunay Allison Voisin Rachel Guiton Christelle Damon-Soubeyrant Yoan Renaud Angélique De Haze Vincent Sapin Anne Fogli Amandine Rambur Cyrille De Joussineau Ayhan Kocer Amalia Trousson Joëlle Henry-Berger Marcus Höring Gerhard Liebisch Silke Matysik Jean-Marc A Lobaccaro Laurent Morel Silvère Baron Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia. PLoS Biology |
| title | Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia. |
| title_full | Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia. |
| title_fullStr | Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia. |
| title_full_unstemmed | Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia. |
| title_short | Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia. |
| title_sort | absence of nuclear receptors lxrs impairs immune response to androgen deprivation and leads to prostate neoplasia |
| url | https://doi.org/10.1371/journal.pbio.3000948 |
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