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

Antognelli, Cinzia; Marinucci, Lorella; Frosini, Roberta; Macchioni, Lara; Talesa, Vincenzo Nicola

doi:10.3390/ijms221910191

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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

by

Cinzia Antognelli

^1,*

,

Lorella Marinucci

¹,

Roberta Frosini

¹,

Lara Macchioni

²

and

Vincenzo Nicola Talesa

¹

Department of Medicine and Surgery, Bioscience and Medical Embryology Division, University of Perugia, L. Severi Square, 06129 Perugia, Italy

²

Department of Medicine and Surgery, Biochemistry and Physiology Division, University of Perugia, L. Severi Square, 06129 Perugia, Italy

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(19), 10191; https://doi.org/10.3390/ijms221910191

Submission received: 23 August 2021 / Revised: 9 September 2021 / Accepted: 16 September 2021 / Published: 22 September 2021

(This article belongs to the Special Issue Prostate Cancer: Stroma Implication in Progression, Diagnosis and Prognosis)

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Abstract

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.

Keywords: methylglyoxal; prostate cancer; bone metastases; osteoblasts; ROS; RAGE; NF-kB

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MDPI and ACS Style

Antognelli, C.; Marinucci, L.; Frosini, R.; Macchioni, L.; Talesa, V.N. 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. Int. J. Mol. Sci. 2021, 22, 10191. https://doi.org/10.3390/ijms221910191

AMA Style

Antognelli C, Marinucci L, Frosini R, Macchioni L, Talesa VN. 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. 2021; 22(19):10191. https://doi.org/10.3390/ijms221910191

Chicago/Turabian Style

Antognelli, Cinzia, Lorella Marinucci, Roberta Frosini, Lara Macchioni, and Vincenzo Nicola Talesa. 2021. "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 22, no. 19: 10191. https://doi.org/10.3390/ijms221910191

APA Style

Antognelli, C., Marinucci, L., Frosini, R., Macchioni, L., & Talesa, V. N. (2021). 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, 22(19), 10191. https://doi.org/10.3390/ijms221910191

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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

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