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Article

Acetylcholine Sustains LNCaP Prostate Cancer Cell Migration, Invasion and Proliferation Through Glyoxalase 1/MG-H1 Axis with the Involvement of Osteopontin

by
Dominga Manfredelli
1,
Tatiana Armeni
2,
Lidia de Bari
3,
Andrea Scirè
4,
Vincenzo Nicola Talesa
1,
Cinzia Antognelli
1,* and
Marilena Pariano
1
1
Department of Medicine and Surgery, Università Degli Studi di Perugia, 06129 Perugia, Italy
2
Department of Life and Environmental Sciences (Di.S.V.A.), Università Politecnica delle Marche, 60131 Ancona, Italy
3
Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), 70126 Bari, Italy
4
Department of Odontostomatologic and Specialized Clinical Sciences, Università Politecnica delle Marche, 60131 Ancona, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(9), 4107; https://doi.org/10.3390/ijms26094107
Submission received: 22 February 2025 / Revised: 23 April 2025 / Accepted: 24 April 2025 / Published: 25 April 2025
(This article belongs to the Special Issue The Role of Extracellular Matrix Proteins in Pathogenesis: 2nd Edition)
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Abstract

The neurotransmitter acetylcholine (ACh) plays a pro-carcinogenic role in various cancer types, including prostate cancer (PCa). The existing body of knowledge concerning the mechanisms that underpin the protumoral role of ACh in PCa is limited. Glyoxalase 1 (Glo1) is a metabolic enzyme that removes methylglyoxal (MG), an endogenous post-translational modification agent, generating 5-hydro-5-methylimidazolone (MG-H1). The Glo1/MG-H1 axis is involved in PCa tumorigenesis and progression. By using LNCaP and PC3 PCa cells, representing extensively studied cell models of poorly aggressive and bone metastasis-derived PCa, respectively, we found that ACh specifically sustains LNCaP cell migration, invasion and proliferation through Glo1-dependent MG-H1 accumulation with the involvement of osteopontin (OPN), thus providing a novel mechanism underlying ACh’s protumoral role in PCa cells. The findings of this study unveil a hitherto unidentified mechanism implicated in the progression of PCa, which is initiated by ACh and involves both the Glo1/MG-H1 axis and OPN. This discovery provides the basis for new avenues of in vivo investigation into the physiological relevance of the roles of the ACh-driven Glo1/MG-H1 axis and OPN in PCa progression and for further research aimed at exploring new ways of managing PCa progression, with the aim of preventing the disease from becoming incurable.
Keywords: acetylcholine; Glyoxalase 1; osteopontin; MG-H1; prostate cancer; LNCaP; migration; invasion acetylcholine; Glyoxalase 1; osteopontin; MG-H1; prostate cancer; LNCaP; migration; invasion

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MDPI and ACS Style

Manfredelli, D.; Armeni, T.; de Bari, L.; Scirè, A.; Talesa, V.N.; Antognelli, C.; Pariano, M. Acetylcholine Sustains LNCaP Prostate Cancer Cell Migration, Invasion and Proliferation Through Glyoxalase 1/MG-H1 Axis with the Involvement of Osteopontin. Int. J. Mol. Sci. 2025, 26, 4107. https://doi.org/10.3390/ijms26094107

AMA Style

Manfredelli D, Armeni T, de Bari L, Scirè A, Talesa VN, Antognelli C, Pariano M. Acetylcholine Sustains LNCaP Prostate Cancer Cell Migration, Invasion and Proliferation Through Glyoxalase 1/MG-H1 Axis with the Involvement of Osteopontin. International Journal of Molecular Sciences. 2025; 26(9):4107. https://doi.org/10.3390/ijms26094107

Chicago/Turabian Style

Manfredelli, Dominga, Tatiana Armeni, Lidia de Bari, Andrea Scirè, Vincenzo Nicola Talesa, Cinzia Antognelli, and Marilena Pariano. 2025. "Acetylcholine Sustains LNCaP Prostate Cancer Cell Migration, Invasion and Proliferation Through Glyoxalase 1/MG-H1 Axis with the Involvement of Osteopontin" International Journal of Molecular Sciences 26, no. 9: 4107. https://doi.org/10.3390/ijms26094107

APA Style

Manfredelli, D., Armeni, T., de Bari, L., Scirè, A., Talesa, V. N., Antognelli, C., & Pariano, M. (2025). Acetylcholine Sustains LNCaP Prostate Cancer Cell Migration, Invasion and Proliferation Through Glyoxalase 1/MG-H1 Axis with the Involvement of Osteopontin. International Journal of Molecular Sciences, 26(9), 4107. https://doi.org/10.3390/ijms26094107

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