Neutrophil gelatinase- associated lipocalin as a screening test in prostate cancer

Muşlu, Necati; Ercan, Bahadır; Akbayir, Serin; Balcı, Şenay; Ovla, Havva Didem; Bozlu, Murat

doi:10.5152/tud.2016.08941

Cited by 4 publications

(4 citation statements)

References 32 publications

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“…In particular, for PCa, its overexpression increased migration and invasion 31,32 ; whereas attenuation of its expression in the PCa cells decreased these processes 33,34 . Lipocalin‐2 was even considered as a screening test for PCa 35 . Microseminoprotein‐β (MSMB)/Prostate secretory protein of 94 amino acids (PSP94), primarily found in the prostatic secretion, was originally isolated and purified from human seminal plasma.…”

Section: Discussionmentioning

confidence: 99%

“…33,34 Lipocalin-2 was even considered as a screening test for PCa. 35 Microseminoprotein-β (MSMB)/Prostate secretory protein of 94 amino acids (PSP94), primarily found in the prostatic secretion, was originally isolated and purified from human seminal plasma. Recent studies have suggested that loss of its expression was associated with PCa aggressiveness.…”

Section: Validation Of Differential Expression Of Selected Genes Anmentioning

confidence: 99%

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Proteomic and transcriptomic profiling of Pten gene‐knockout mouse model of prostate cancer

Zhang

Kim

et al. 2020

The Prostate

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Background The prostate‐specific phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene‐conditional knockout (KO) mouse carcinogenesis model is highly desirable for studies of prostate cancer biology and chemoprevention due to its close resemblance of primary molecular defect and many histopathological features of human prostate cancer including androgen response and disease progression from prostatic intraepithelial neoplasia to invasive adenocarcinoma. Here, we profiled the proteome and transcriptome of the Pten‐KO mouse prostate tumors for global macromolecular expression alterations for signaling changes and biomarker signatures. Methods For proteomics, four pairs of whole prostates from tissue‐specific conditional knockout Pten‐KO mice (12‐15 weeks of age) and their respective wild‐type littermates housed in the same cages were analyzed by 8‐plex isobaric tags for relative and absolute quantitation iTRAQ. For microarray transcriptomic analysis, three additional matched pairs of prostate/tumor specimens from respective mice at 20 to 22 weeks of age were used. Real‐time quantitative reverse transcription‐polymerase chain reaction was used to verify the trends of protein and RNA expression changes. Gene Set Enrichment Analysis and Ingenuity Pathway Analysis were carried out for bioinformatic characterizations of pathways and networks. Results At the macromolecular level, proteomic and transcriptomic analyses complement and cross‐validate to reveal overexpression signatures including inflammation and immune alterations, in particular, neutrophil/myeloid lineage suppressor cell features, chromatin/histones, ion and nutrient transporters, and select glutathione peroxidases and transferases in Pten‐KO prostate tumors. Suppressed expression patterns in the Pten‐KO prostate tumors included glandular differentiation such as secretory proteins and androgen receptor targets, smooth muscle features, and endoplasmic reticulum stress proteins. Bioinformatic analyses identified immune and inflammation responses as the most profound macromolecular landscape changes, and the predicted key nodal activities through Akt, nuclear factor‐kappaB, and P53 in the Pten‐KO prostate tumor. Comparison with other genetically modified mouse prostate carcinogenesis models revealed notable molecular distinctions, especially the dominance of immune and inflammation features in the Pten‐KO prostate tumors. Conclusions Our work identified prominent macromolecular signatures and key nodal molecules that help to illuminate the patho‐ and immunobiology of Pten‐loss driven prostate cancer and can facilitate the choice of biomarkers for chemoprevention and interception studies in this clinically relevant mouse prostate cancer model.

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Section: Discussionmentioning

confidence: 99%

Section: Validation Of Differential Expression Of Selected Genes Anmentioning

confidence: 99%

Proteomic and transcriptomic profiling of Pten gene‐knockout mouse model of prostate cancer

Zhang

Kim

et al. 2020

The Prostate

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“…Interestingly, the expression of both LNC2 and MMP9 genes was increased in 16 tumor types, demonstrating their involvement in tumor development. This result was consistent with those reported in the literature for several tumors, including BLCA ( Ricci et al, 2015 ; Candido et al, 2016b ), CESC ( Li et al, 2012 ), CHOL ( Leelawat et al, 2011 ; Nair et al, 2018 ; Li et al, 2019 ), ESCA ( Zhang et al, 2007 ), HNSC ( Ruokolainen et al, 2005 ; Hiromoto et al, 2011 ; Stanciu et al, 2016 ; Verma et al, 2017 ), KIRP ( Cho et al, 2003 ; Zhang et al, 2015 ), LIHC ( Chen et al, 2012 ; Abdelsameea et al, 2020 ), LUAD ( Ruiz-Morales et al, 2015 ), OV ( Cho and Kim, 2009 ; Gupta et al, 2022 ); PAAD ( Kaur et al, 2013 ), STAD ( Du et al, 2011 ), UCEC ( Cymbaluk-Płoska et al, 2017 ), COAD ( Yang et al, 2014 ; Ozemir et al, 2016 ; Liang and Chang, 2018 ), LUSC ( Lee et al, 2015 ), PRAD ( Ma et al, 2017 ; Muşlu et al, 2017 ; Ulusoy et al, 2021 ), READ ( Zhang et al, 2009 ; Annaházi et al, 2016 ), and THCA ( Barresi et al, 2012 ; Liu et al, 2019 ; Xu et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis of the LCN2–SLC22A17–MMP9 network in cancer: The role of DNA methylation in the modulation of tumor microenvironment

Candido

Tomasello

Lavoro

et al. 2022

Front. Cell Dev. Biol.

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Several features of cancer cells such as proliferation, invasion, metastatic spreading, and drug resistance are affected by their interaction with several tumor microenvironment (TME) components, including neutrophil gelatinase-associated lipocalin (NGAL), solute carrier family 22 member 17 (SLC22A17), and matrix metallopeptidase 9 (MMP9). These molecules play a key role in tumor growth, invasion, and iron-dependent metabolism of cancer cells. However, the precise epigenetic mechanisms underlying the gene regulation of Lipocalin 2 (LCN2), SLC22A17, and MMP9 in cancer still remain unclear. To this purpose, computational analysis was performed on TCGA and GTEx datasets to evaluate the expression and DNA methylation status of LCN2, SLC22A17, and MMP9 genes in different tumor types. Correlation analysis between gene/isoforms expression and DNA methylation levels of LCN2, SLC22A17, and MMP9 was performed to investigate the role of DNA methylation in the modulation of these genes. Protein network analysis was carried out using reverse phase protein arrays (RPPA) data to identify protein–protein interactions of the LCN2–SLC22A17–MMP9 network. Furthermore, survival analysis was performed according to gene expression and DNA methylation levels. Our results demonstrated that LCN2 and MMP9 were mainly upregulated in most tumor types, whereas SLC22A17 was largely downregulated, representing a specific hallmark signature for all gastrointestinal tumors. Notably, the expression of LCN2, SLC22A17, and MMP9 genes was negatively affected by promoter methylation. Conversely, intragenic hypermethylation was associated with the overexpression of SLC22A17 and MMP9 genes. Protein network analysis highlighted the role of the LCN2–SLC22A17–MMP9 network in TME by the interaction with fibronectin 1 and claudin 7, especially in rectal tumors. Moreover, the impact of expression and methylation status of LCN2, SLC22A17, and MMP9 on overall survival and progression free interval was tumor type–dependent. Overall, our analyses provide a detailed overview of the expression and methylation status of LCN2, SLC22A17, and MMP9 in all TCGA tumors, indicating that the LCN2–SLC22A17–MMP9 network was strictly regulated by DNA methylation within TME. Our findings pave the way for the identification of novel DNA methylation hotspots with diagnostic and prognostic values and suitable for epi-drug targeting.

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“…The fact that LCN2 is secreted makes it particularly suitable as a potential non-invasive biomarker. Indeed, LCN2 has been detected in urine and serum of PCa patients [ 16 , 20 , 21 , 22 , 23 , 24 ]. Nevertheless, the underlying cellular and molecular mechanisms on how LCN2 affects PCa tumorigenesis are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Lipocalin-2 (LCN2) Deficiency Leads to Cellular Changes in Highly Metastatic Human Prostate Cancer Cell Line PC-3

Schröder

Pinoé-Schmidt

Weiskirchen

2022

Cells

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The transporter protein lipocalin-2 (LCN2) also termed neutrophil-gelatinase-associated lipocalin (NGAL) has pleiotropic effects in tumorigenesis in various cancers. Since the precise role of LCN2 in prostate cancer (PCa) is poorly understood, we aimed to elucidate its functions in PCa in vitro. For this purpose, LCN2 was transiently suppressed or permanently depleted in human PC-3 cells using siRNA or CRISPR/Cas9-mediated knockout. Effects of LCN2 suppression on expression of different tumorigenic markers were investigated by Western blot analysis and RT-qPCR. LCN2 knockout cells were analyzed for cellular changes and their ability to cope endoplasmic stress compared to parenteral PC-3 cells. Reduced LCN2 was accompanied by decreased expression of IL-1β and Cx43. In PC-3 cells, LCN2 deficiency leads to reduced proliferation, diminished expression of pro-inflammatory cytokines, lower adhesion, and disrupted F-actin distribution. In addition, IL-1β expression strongly correlated with LCN2 levels. LCN2 knockout cells showed enhanced and sustained activation of unfolded protein response proteins when treated with tunicamycin or cultured under glucose deprivation. Interestingly, an inverse correlation between phosphorylation of eukaryotic initiation factor 2 α subunit (p-eIF2α) and LCN2 expression was observed suggesting that LCN2 triggers protein synthesis under stress conditions. The finding that LCN2 depletion leads to significant phenotypic and cellular changes in PC-3 cells adds LCN2 as a valuable target for the treatment of PCa.

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Neutrophil gelatinase- associated lipocalin as a screening test in prostate cancer

Cited by 4 publications

References 32 publications

Proteomic and transcriptomic profiling of Pten gene‐knockout mouse model of prostate cancer

Proteomic and transcriptomic profiling of Pten gene‐knockout mouse model of prostate cancer

Bioinformatic analysis of the LCN2–SLC22A17–MMP9 network in cancer: The role of DNA methylation in the modulation of tumor microenvironment

Lipocalin-2 (LCN2) Deficiency Leads to Cellular Changes in Highly Metastatic Human Prostate Cancer Cell Line PC-3

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