Implication and role of neutrophil gelatinase-associated lipocalin in cancer: lipocalin-2 as a potential novel emerging comprehensive therapeutic target for a variety of cancer types

Rahimi, Sina; Roushandeh, Amaneh Mohammadi; Ahmadzadeh, Ebrahim; Jahanian-Najafabadi, Ali; Roudkenar, Mehryar Habibi

doi:10.1007/s11033-020-05261-5

Cited by 29 publications

(22 citation statements)

References 141 publications

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“…Finally, the CLUSTER S/SEV OSCC_LNM was specifically associated to GO groups related to activities against pathogen agents, such as "metal sequestration by antimicrobial proteins" (associated to LCN2, LTF, S100A9-see Table 6 for the FC in S/SEV OSCC_LNM); "growth of symbiont in host" (associated to ELANE, MPO, PGLYRP1-see Table 6 for the FC in S/SEV OSCC_LNM); and "antimicrobial peptides" (associated to ELANE, GAPDH, LCN2, LTF, MPO, PGLYRP1, PI3, PRTN3, RNASE3, S100A12, S100A9-see Table 6 for the FC in S/SEV OSCC_LNM). Proteins of these groups, such as lactoferrin (LFT,), lipocalin-2 (LCN2), S100A9 (forming with S100A8 the heterodimeric complex calprotectin), neutrophil elastase (ELANE), peptidoglycan recognition protein 1 (PGLYRP1), and myeloperoxidase (MPO), are widely described for their antibacterial activity or for their role as inflammatory markers [44][45][46][47][48]. The enrichment of these proteins in the S/SEVs from patients with OSCC_LNM could be indicative of dysbiotic signatures occurring during tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Protein Cargo of Salivary Small Extracellular Vesicles as Potential Functional Signature of Oral Squamous Cell Carcinoma

Fontana

Mauceri

Novara

et al. 2021

IJMS

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The early diagnosis of oral squamous cell carcinoma (OSCC) is still an investigative challenge. Saliva has been proposed as an ideal diagnostic medium for biomarker detection by mean of liquid biopsy technique. The aim of this pilot study was to apply proteomic and bioinformatic strategies to determine the potential use of saliva small extracellular vesicles (S/SEVs) as a potential tumor biomarker source. Among the twenty-three enrolled patients, 5 were free from diseases (OSCC_FREE), 6 were with OSCC without lymph node metastasis (OSCC_NLNM), and 12 were with OSCC and lymph node metastasis (OSCC_LNM). The S/SEVs from patients of each group were pooled and properly characterized before performing their quantitative proteome comparison based on the SWATH_MS (Sequential Window Acquisition of all Theoretical Mass Spectra) method. The analysis resulted in quantitative information for 365 proteins differentially characterizing the S/SEVs of analyzed clinical conditions. Bioinformatic analysis of the proteomic data highlighted that each S/SEV group was associated with a specific cluster of enriched functional network terms. Our results highlighted that protein cargo of salivary small extracellular vesicles defines a functional signature, thus having potential value as novel predict biomarkers for OSCC.

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Section: Discussionmentioning

confidence: 99%

Protein Cargo of Salivary Small Extracellular Vesicles as Potential Functional Signature of Oral Squamous Cell Carcinoma

Fontana

Mauceri

Novara

et al. 2021

IJMS

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“…LCN2 is known to play dual roles in mediating the progression of tumorigenesis. One role involves the promotion of tumorigenesis by increasing cell proliferation, the metastatic potential and independent predictor for severity of grades and stages of tumors [ 26 , 27 ]. In vitro and in vivo studies have shown that LCN2 promotes cell invasion and migration and distant metastasis in prostate cancer via the ERK signaling pathway, causing up-regulation of the SLUG transcription factor to induce the EMT [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Lipocalin-2 Inhibits Proliferation and Invasiveness of Human Glioblastoma Multiforme Cells by Activating ERK Targeting Cathepsin D Expression

Hsieh

Tsai²,

et al. 2021

Biology

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Lipocalin-2 (LCN2) exhibits pro- and anti-carcinogenic effects in several cancers, but its role in the progression of glioblastoma multiforme (GBM) remains unclear. This study aims to elucidate the effect of LCN2 in human GBM cell, and the mechanism underlying its effects on GBM malignant progression. We observed that LCN2 expression was significantly lower in GBM than in normal tissues and was associated with poorer GBM patient survival. LCN2-overexpressing GBM cells showed significantly reduced proliferation and migration/invasion abilities. Human protease antibody array analysis showed that the expression of cathepsin D (CTSD) protein and mRNA was lower in LCN2-overexpressing GBM cells than in controls. Higher CTSD expression was observed in GBM tumors than in normal tissues, and higher CTSD expression was associated with poorer overall and disease-free survival. LCN2-overexpressing GBM cells exhibited increased ERK phosphorylation. Treatment of these cells with a MEK inhibitor (U0126) restored CTSD expression, cell migration, and cell invasiveness. In conclusion, LCN2 might be serving as a prognostic marker and promising anti-proliferative and anti-metastatic target for treating GBM.

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“…Lcn-2/ NGAL, is a member of the lipocalin family, which shares a tight tertiary structure, and ligand binding and post-translational modifications in Lcn-2 leads to diverse Lcn-2 functions (87). Lcn-2 is considered a therapeutic target for AKI, CKD and numerous types of cancer such as breast, esophagus and liver cancer (87)(88)(89). Lcn-2 plays a pivotal role in various kidney diseases, such as sepsis and IR (90).…”

Section: Macrophage-derived Mediators In Akimentioning

confidence: 99%

Major signaling pathways and key mediators of macrophages in acute kidney injury (Review)

Chen

Wang³

et al. 2021

Mol Med Rep

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Acute kidney injury (AKI) has become a global public health problem with high morbidity and mortality rates, as well as high healthcare costs. Immune cells, particularly macrophages, which regulate tissue development, destroy pathogens, control homeostasis and repair wounds, play crucial and complex roles in AKI. In various types of AKI, numerous rapidly recruited monocytes and tissue-resident macrophages act in a coordinated manner. Thus, elucidating the phenotypic and functional characteristics of macrophages in AKI is essential for identifying potential therapeutic targets. Macrophage-sensing mediators and macrophage-derived mediators participate in the major macrophage-related signaling pathways in AKI, which regulate macrophage polarization and determine disease progression. In conclusion, macrophages change their roles and regulatory mechanisms during the occurrence and development of AKI. The aim of the present review was to contribute to an improved understanding of AKI and to the identification of novel therapeutic targets for this condition.

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Implication and role of neutrophil gelatinase-associated lipocalin in cancer: lipocalin-2 as a potential novel emerging comprehensive therapeutic target for a variety of cancer types

Cited by 29 publications

References 141 publications

Protein Cargo of Salivary Small Extracellular Vesicles as Potential Functional Signature of Oral Squamous Cell Carcinoma

Protein Cargo of Salivary Small Extracellular Vesicles as Potential Functional Signature of Oral Squamous Cell Carcinoma

Overexpression of Lipocalin-2 Inhibits Proliferation and Invasiveness of Human Glioblastoma Multiforme Cells by Activating ERK Targeting Cathepsin D Expression

Major signaling pathways and key mediators of macrophages in acute kidney injury (Review)

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