Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases
Bone metastases from prostate cancer (PCa) result from a complex cross-talk between PCa cells and osteoblasts (OB). Thus, targeting this interplay has become an attractive strategy to interfere with PCa bone dissemination. The agents currently used in clinical trials have proved ineffective, boostin...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/19/10191 |
| _version_ | 1797516451657023488 |
|---|---|
| author | Cinzia Antognelli Lorella Marinucci Roberta Frosini Lara Macchioni Vincenzo Nicola Talesa |
| author_facet | Cinzia Antognelli Lorella Marinucci Roberta Frosini Lara Macchioni Vincenzo Nicola Talesa |
| author_sort | Cinzia Antognelli |
| collection | DOAJ |
| description | Bone metastases from prostate cancer (PCa) result from a complex cross-talk between PCa cells and osteoblasts (OB). Thus, targeting this interplay has become an attractive strategy to interfere with PCa bone dissemination. The agents currently used in clinical trials have proved ineffective, boosting research to identify additional mechanisms that may be involved in this two-directional talk. Here, we investigated whether and how 5-hydro-5-methylimidazolone (MG-H1), a specific methylglyoxal (MG)-derived advanced glycation end product (AGE), was a novel player in the dialogue between PCa and OB to drive PCa bone metastases. Conditioned medium from osteotropic PC3 PCa cells, pre-treated or not with a specific MG scavenger, was administrated to human primary OB and cell morphology, mesenchymal trans-differentiation, pro-osteogenic determinants, PCa-specific molecules, and migration/invasion were studied by phase-contrast microscopy, real-time PCR, western blot and specific assays, respectively. We found that PC3 cells were able to release MG-H1 that, by binding to the receptor for AGEs (RAGE) on OB, reprogrammed them into a less-differentiate phenotype, endowed with some PCa-specific molecular features and malignant properties, in a mechanism involving reactive oxidative species (ROS) production and NF-kB pathway activation. These findings provide novel insights into the mechanisms of PCa osteoblastic metastases and foster in vivo research toward new therapeutic strategies interfering with PCa/OB cross-talk. |
| first_indexed | 2024-03-10T07:01:15Z |
| format | Article |
| id | doaj.art-f3d6ac72492f430ca74d75e67a467249 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:01:15Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f3d6ac72492f430ca74d75e67a4672492023-11-22T16:05:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191019110.3390/ijms221910191Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone MetastasesCinzia Antognelli0Lorella Marinucci1Roberta Frosini2Lara Macchioni3Vincenzo Nicola Talesa4Department of Medicine and Surgery, Bioscience and Medical Embryology Division, University of Perugia, L. Severi Square, 06129 Perugia, ItalyDepartment of Medicine and Surgery, Bioscience and Medical Embryology Division, University of Perugia, L. Severi Square, 06129 Perugia, ItalyDepartment of Medicine and Surgery, Bioscience and Medical Embryology Division, University of Perugia, L. Severi Square, 06129 Perugia, ItalyDepartment of Medicine and Surgery, Biochemistry and Physiology Division, University of Perugia, L. Severi Square, 06129 Perugia, ItalyDepartment of Medicine and Surgery, Bioscience and Medical Embryology Division, University of Perugia, L. Severi Square, 06129 Perugia, ItalyBone metastases from prostate cancer (PCa) result from a complex cross-talk between PCa cells and osteoblasts (OB). Thus, targeting this interplay has become an attractive strategy to interfere with PCa bone dissemination. The agents currently used in clinical trials have proved ineffective, boosting research to identify additional mechanisms that may be involved in this two-directional talk. Here, we investigated whether and how 5-hydro-5-methylimidazolone (MG-H1), a specific methylglyoxal (MG)-derived advanced glycation end product (AGE), was a novel player in the dialogue between PCa and OB to drive PCa bone metastases. Conditioned medium from osteotropic PC3 PCa cells, pre-treated or not with a specific MG scavenger, was administrated to human primary OB and cell morphology, mesenchymal trans-differentiation, pro-osteogenic determinants, PCa-specific molecules, and migration/invasion were studied by phase-contrast microscopy, real-time PCR, western blot and specific assays, respectively. We found that PC3 cells were able to release MG-H1 that, by binding to the receptor for AGEs (RAGE) on OB, reprogrammed them into a less-differentiate phenotype, endowed with some PCa-specific molecular features and malignant properties, in a mechanism involving reactive oxidative species (ROS) production and NF-kB pathway activation. These findings provide novel insights into the mechanisms of PCa osteoblastic metastases and foster in vivo research toward new therapeutic strategies interfering with PCa/OB cross-talk.https://www.mdpi.com/1422-0067/22/19/10191methylglyoxalprostate cancerbone metastasesosteoblastsROSRAGE |
| spellingShingle | Cinzia Antognelli Lorella Marinucci Roberta Frosini Lara Macchioni Vincenzo Nicola Talesa Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases International Journal of Molecular Sciences methylglyoxal prostate cancer bone metastases osteoblasts ROS RAGE |
| title | Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases |
| title_full | Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases |
| title_fullStr | Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases |
| title_full_unstemmed | Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases |
| title_short | Metastatic Prostate Cancer Cells Secrete Methylglyoxal-Derived MG-H1 to Reprogram Human Osteoblasts into a Dedifferentiated, Malignant-like Phenotype: A Possible Novel Player in Prostate Cancer Bone Metastases |
| title_sort | metastatic prostate cancer cells secrete methylglyoxal derived mg h1 to reprogram human osteoblasts into a dedifferentiated malignant like phenotype a possible novel player in prostate cancer bone metastases |
| topic | methylglyoxal prostate cancer bone metastases osteoblasts ROS RAGE |
| url | https://www.mdpi.com/1422-0067/22/19/10191 |
| work_keys_str_mv | AT cinziaantognelli metastaticprostatecancercellssecretemethylglyoxalderivedmgh1toreprogramhumanosteoblastsintoadedifferentiatedmalignantlikephenotypeapossiblenovelplayerinprostatecancerbonemetastases AT lorellamarinucci metastaticprostatecancercellssecretemethylglyoxalderivedmgh1toreprogramhumanosteoblastsintoadedifferentiatedmalignantlikephenotypeapossiblenovelplayerinprostatecancerbonemetastases AT robertafrosini metastaticprostatecancercellssecretemethylglyoxalderivedmgh1toreprogramhumanosteoblastsintoadedifferentiatedmalignantlikephenotypeapossiblenovelplayerinprostatecancerbonemetastases AT laramacchioni metastaticprostatecancercellssecretemethylglyoxalderivedmgh1toreprogramhumanosteoblastsintoadedifferentiatedmalignantlikephenotypeapossiblenovelplayerinprostatecancerbonemetastases AT vincenzonicolatalesa metastaticprostatecancercellssecretemethylglyoxalderivedmgh1toreprogramhumanosteoblastsintoadedifferentiatedmalignantlikephenotypeapossiblenovelplayerinprostatecancerbonemetastases |