Prolactin‐ and testosterone‐induced carboxypeptidase‐D correlates with increased nitrotyrosines and Ki67 in prostate cancer

Thomas, Lynn N.; Merrimen, Jennifer; Bell, David; Rendon, Ricardo; Too, Catherine K.L.

doi:10.1002/pros.23054

Cited by 17 publications

(10 citation statements)

References 68 publications

(105 reference statements)

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“…RNS Neutralization Sensitizes CRPC to Immunotherapy. There is significant up-regulation of 3-NT in human prostate cancer (6)(7)(8)(9), consistent with the abundant tumor-infiltrating MDSCs in clinical prostate cancer (21). To assess 3-NT in CRPC, we performed immunohistochemistry (IHC) of 3-NT for a small set of human primary CRPC samples (n = 15) and observed that while adjacent normal-like prostate stained negatively, 40% (6/15) of CPRC cases stained positively (Fig.…”

Section: Resultssupporting

confidence: 53%

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Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers

Feng

Cheng

Zhang

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

114

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Potent immunosuppressive mechanisms within the tumor microenvironment contribute to the resistance of aggressive human cancers to immune checkpoint blockade (ICB) therapy. One of the main mechanisms for myeloid-derived suppressor cells (MDSCs) to induce T cell tolerance is through secretion of reactive nitrogen species (RNS), which nitrates tyrosine residues in proteins involved in T cell function. However, so far very few nitrated proteins have been identified. Here, using a transgenic mouse model of prostate cancer and a syngeneic cell line model of lung cancer, we applied a nitroproteomic approach based on chemical derivation of 3-nitrotyrosine and identified that lymphocyte-specific protein tyrosine kinase (LCK), an initiating tyrosine kinase in the T cell receptor signaling cascade, is nitrated at Tyr394 by MDSCs. LCK nitration inhibits T cell activation, leading to reduced interleukin 2 (IL2) production and proliferation. In human T cells with defective endogenous LCK, wild type, but not nitrated LCK, rescues IL2 production. In the mouse model of castration-resistant prostate cancer (CRPC) by prostate-specific deletion of ,, and , CRPC is resistant to an ICB therapy composed of antiprogrammed cell death 1 (PD1) and anticytotoxic-T lymphocyte-associated protein 4 (CTLA4) antibodies. However, we showed that ICB elicits strong anti-CRPC efficacy when combined with an RNS neutralizing agent. Together, these data identify a previously unknown mechanism of T cell inactivation by MDSC-induced protein nitration and illuminate a clinical path hypothesis for combining ICB with RNS-reducing agents in the treatment of CRPC.

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Section: Resultssupporting

confidence: 53%

“…Protein nitration, a form of posttranslational modification, usually occurs at the 3′-position of the phenolic ring of tyrosine (Tyr) to form 3-nitrotyrosine (3-NT). Up-regulation of 3-NT is documented in various human cancers, including prostate cancer (6)(7)(8)(9). In MDSCs, both endothelial NO synthase (eNOS) and iNOS contribute to the production of NO.…”

mentioning

confidence: 99%

Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers

Feng

Cheng

Zhang

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

114

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“…Inducible nitric oxide synthase (iNOS) has been reported to influence malignant behaviors, including cell proliferation and invasion, by inducing the accumulation of mutations in p53, enrichment of basal-like gene signature, transactivation of the epidermal growth factor receptor, activation of NF-κB, and increased secretion of pro-inflammatory cytokines in malignancies, including PC [125,126]. One study showed that the oral administration of EGCG decreased iNOS activity in the ventral prostate of TRAMP mice [40].…”

Section: Anti-cancer Effects Of Green Tea At the Molecular Levelmentioning

confidence: 99%

Anti-Cancer Effects of Green Tea Polyphenols Against Prostate Cancer

et al. 2019

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Prostate cancer is the most common cancer among men. Green tea consumption is reported to play an important role in the prevention of carcinogenesis in many types of malignancies, including prostate cancer; however, epidemiological studies show conflicting results regarding these anti-cancer effects. In recent years, in addition to prevention, many investigators have shown the efficacy and safety of green tea polyphenols and combination therapies with green tea extracts and anti-cancer agents in in vivo and in vitro studies. Furthermore, numerous studies have revealed the molecular mechanisms of the anti-cancer effects of green tea extracts. We believe that improved understanding of the detailed pathological roles at the molecular level is important to evaluate the prevention and treatment of prostate cancer. Therefore, in this review, we present current knowledge regarding the anti-cancer effects of green tea extracts in the prevention and treatment of prostate cancer, with a particular focus on the molecular mechanisms of action, such as influencing tumor growth, apoptosis, androgen receptor signaling, cell cycle, and various malignant behaviors. Finally, the future direction for the use of green tea extracts as treatment strategies in patients with prostate cancer is introduced.

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“…Aaltoma et al also demonstrated a positive association between expression level of iNOS and rapid cancer cell proliferation rate, dedifferentiation and advanced stage cancer [113]. A recent study has shown that NO also regulated cell proliferation in a pathway of CPD-Arg-NO [114].…”

Section: Nos and Proliferation Of Prostate Carcinomamentioning

confidence: 99%

Nitric Oxide Synthase in Male Urological and Andrologic Functions

Yu¹,

Li²,

Li³

et al. 2017

Nitric Oxide Synthase - Simple Enzyme-Complex Roles

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Nitric oxide (NO), a crucial signaling molecule, is synthesized by the nitric oxide synthase (NOS) enzyme. The significant effects of NOS are under exploration, and the roles of potential therapy targets for diseases of NOS are widely accepted. In this chapter, we summarized the important roles of NOS mainly on pathogenesis of prostate diseases, male infertility, erectile dysfunction and, addition, the potential therapeutic efficacies of NOS for those diseases.

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Prolactin‐ and testosterone‐induced carboxypeptidase‐D correlates with increased nitrotyrosines and Ki67 in prostate cancer

Cited by 17 publications

References 68 publications

Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers

Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers

Anti-Cancer Effects of Green Tea Polyphenols Against Prostate Cancer

Nitric Oxide Synthase in Male Urological and Andrologic Functions

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