Glyoxalase-1-Dependent Methylglyoxal Depletion Sustains PD-L1 Expression in Metastatic Prostate Cancer Cells: A Novel Mechanism in Cancer Immunosurveillance Escape and a Potential Novel Target to Overcome PD-L1 Blockade Resistance

Antognelli, Cinzia; Mandarano, Martina; Prosperi, Enrico; Sidoni, Angelo; Talesa, Vincenzo Nicola

doi:10.3390/cancers13122965

Cited by 16 publications

(15 citation statements)

References 74 publications

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“…Elevation of MG concentration in ATC is coexistent with a decrease in activity of glutathione-glyoxalase 1 (Glo-1). The role of MG and Glo1 seems to be dependent on cancer type, since cancer tissues and cell lines of different molecular background and MG detoxication rate react differently under stress caused by MG [148]. Another in vitro study confirmed that the invasive/migration properties of model ATC cells were associated with accumulation of MG adducts and implementation of aminoguanidine, and that resveratrol decreased the amount of MG adducts.…”

Section: Selected Advanced Glycation End-product Precursors and Rage Ligands As Factors Ofmentioning

confidence: 84%

Role of Advanced Glycation End-Products and Other Ligands for AGE Receptors in Thyroid Cancer Progression

Bronowicka-Szydełko

Kotyra

Lewandowski

et al. 2021

JCM

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To date, thyroid cancers (TCs) remain a clinical challenge owing to their heterogeneous nature. The etiopathology of TCs is associated not only with genetic mutations or chromosomal rearrangements, but also non-genetic factors, such as oxidative-, nitrosative-, and carbonyl stress-related alterations in tumor environment. These factors, through leading to the activation of intracellular signaling pathways, induce tumor tissue proliferation. Interestingly, the incidence of TCs is often coexistent with various simultaneous mutations. Advanced glycation end-products (AGEs), their precursors and receptors (RAGEs), and other ligands for RAGEs are reported to have significant influence on carcinogenesis and TCs progression, inducing gene mutations, disturbances in histone methylation, and disorders in important carcinogenesis-related pathways, such as PI3K/AKT/NF-kB, p21/MEK/MPAK, or JAK/STAT, RAS/ERK/p53, which induce synthesis of interleukins, growth factors, and cytokines, thus influencing metastasis, angiogenesis, and cancer proliferation. Precursors of AGE (such as methylglyoxal (MG)) and selected ligands for RAGEs: AS1004, AS1008, and HMGB1 may, in the future, become potential targets for TCs treatment, as low MG concentration is associated with less aggressive anaplastic thyroid cancer, whereas the administration of anti-RAGE antibodies inhibits the progression of papillary thyroid cancer and anaplastic thyroid cancer. This review is aimed at collecting the information on the role of compounds, engaged in glycation process, in the pathogenesis of TCs. Moreover, the utility of these compounds in the diagnosis and treatment of TCs is thoroughly discussed. Understanding the mechanism of action of these compounds on TCs pathogenesis and progression may potentially be the grounds for the development of new treatment strategies, aiming at quality-of-life improvements.

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Section: Selected Advanced Glycation End-product Precursors and Rage Ligands As Factors Ofmentioning

confidence: 84%

Role of Advanced Glycation End-Products and Other Ligands for AGE Receptors in Thyroid Cancer Progression

Bronowicka-Szydełko

Kotyra

Lewandowski

et al. 2021

JCM

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“…In the last decade, we have demonstrated that Glo1, by scavenging MG and, consequently by preventing MG-derived MG-H1 formation, plays a pivotal role in PCa progression through both apoptosis [ 20 , 21 ] and EMT [ 22 , 23 ] control. Very recently, we have also found that Glo1/MG-H1 axis contributes to maintaining an immunosuppressive microenvironment by modulating PD-L1 expression [ 24 ]. Here, we added further information to the oncogenic role of the Glo1/MG-H1 pathway in PCa, including it among the mechanisms of PCa cells/OB cross-talk essential to guide bone metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…The role of the Glo1/MG-AGEs axis in PCa progression is today well defined [13]. Glo1 is overexpressed in advanced metastatic PCa, where, through specific MG-derived AGEs, it participates in cancer survival [20,21], PTEN/PI3K/AKT/mTOR signaling-and epithelial-to-mesenchymal transition (EMT)-related metastatic behavior [22,23], in addition, contributes to maintaining an immunosuppressive microenvironment through MG-H1mediated PD-L1 up-regulation [24]. Whether Glo1/MG-H1 axis is also implicated in the mechanisms of PCa cells-driven bone metastases has never been investigated before.…”

Section: Introductionmentioning

confidence: 99%

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

Marinucci

Frosini

et al. 2021

IJMS

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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.

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“…Regardless of cancer incidence rate and cell deaths, there have been efforts in developing novel therapeutics for tumor treatment [ 3 , 4 , 5 , 6 ]. Surgery or tumor resection is beneficial in early stages of cancer and when tumor cells diffuse into various tissues in body, it is impossible to eliminate cancer by using surgery [ 7 , 8 ]. Radiotherapy is less invasive compared to surgery, but it has its own problems including side effects and risk of resistance [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

Paskeh

Asadi²,

Zabolian

et al. 2021

IJMS

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As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/β-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.

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Glyoxalase-1-Dependent Methylglyoxal Depletion Sustains PD-L1 Expression in Metastatic Prostate Cancer Cells: A Novel Mechanism in Cancer Immunosurveillance Escape and a Potential Novel Target to Overcome PD-L1 Blockade Resistance

Cited by 16 publications

References 74 publications

Role of Advanced Glycation End-Products and Other Ligands for AGE Receptors in Thyroid Cancer Progression

Role of Advanced Glycation End-Products and Other Ligands for AGE Receptors in Thyroid Cancer Progression

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

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

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