Revisiting Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Cancer: Saint or Sinner?

Bauvois, Brigitte; Susin, Santos A.

doi:10.3390/cancers10090336

Cited by 46 publications

(37 citation statements)

References 86 publications

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“…We and others previously showed that Lcn2 levels are significantly up-regulated in tissues and urine samples from patients with invasive breast cancer (25,(27)(28)(29)(30). We further confirmed that Lcn2 gene expression was significantly up-regulated in human TNBC cell lines (MDA-MB-231 and MDA-MB-436) in comparison with nonneoplastic MCF10A cells (Fig.…”

Section: Deformable Tnlgs Breach In Vitro Tumor Endothelial Barrier Vsupporting

confidence: 84%

Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel

Guo

Yang

Huang

et al. 2019

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

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Triple-negative breast cancer (TNBC), which has the highest mortality rate of all breast cancer, is in urgent need of a therapeutic that hinders the spread and growth of cancer cells. CRISPR genome editing holds the promise of a potential cure for many genetic diseases, including TNBC; however, its clinical translation is being challenged by the lack of safe and effective nonviral delivery systems for in vivo therapeutic genome editing. Here we report the synthesis and application of a noncationic, deformable, and tumor-targeted nanolipogel system (tNLG) for CRISPR genome editing in TNBC tumors. We have demonstrated that tNLGs mediate a potent CRISPR knockout of Lipocalin 2 (Lcn2), a known breast cancer oncogene, in human TNBC cells in vitro and in vivo. The loss of Lcn2 significantly inhibits the migration and the mesenchymal phenotype of human TNBC cells and subsequently attenuates TNBC aggressiveness. In an orthotopic TNBC model, we have shown that systemically administered tNLGs mediated >81% CRISPR knockout of Lcn2 in TNBC tumor tissues, resulting in significant tumor growth suppression (>77%). Our proof-of-principle results provide experimental evidence that tNLGs can be used as a safe, precise, and effective delivery approach for in vivo CRISPR genome editing in TNBC.

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Section: Deformable Tnlgs Breach In Vitro Tumor Endothelial Barrier Vsupporting

confidence: 84%

Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel

Guo

Yang

Huang

et al. 2019

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

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“…There is evidence that NGAL may be a marker of disease status in chronic and acute pathological conditions, especially in inflammatory, metabolic, neurological and cancer diseases (37)(38)(39). Multiple studies have explored the possible role of NGAL in various cancer models and have shown that NGAL has beneficial and harmful functions (37,40).…”

Section: Discussionmentioning

confidence: 99%

NGAL protects in nasopharyngeal carcinoma by inducing apoptosis and blocking epithelial‑mesenchymal transition

et al. 2020

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In recent years, neutrophil gelatinase-associated lipocalin (NGAL) has been considered to be a key molecule in different cancer types and its carcinogenesis may be related to the NGAL/MMP-9 complex. However, its expression pattern and role in nasopharyngeal carcinoma (NPC) has rarely been reported. In the current study, 158 tumor tissues from NPC patients were collected and immunohistochemistry was performed to determine the NGAL protein expression, to investigate the correlation between its expression and clinical and pathological parameters using Chi square analysis. Furthermore, by over-expressing NGAL in NPC cell lines, biological alteration of NPC cells with respect to cell proliferation, migration and invasion was analyzed. Results suggested that high expression of NGAL predicts better prognosis and longer survival. Overexpression of NGAL significantly reduced the proliferation and migration of NPC cells, and induced the apoptosis by activating caspase 3, 8 and 9, and blocking epithelial-mesenchymal transition by inhibiting mothers against decapentaplegic homolog 2/3 phosphorylation.

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“…Lipocalin 2 (LCN2), a member of the lipocalin subfamily, also known as neutrophil gelatinase-associated lipocalin (NGAL), is a 25 kDa secreted glycoprotein (Bauvois and Susin, 2018). NGAL also has other forms in serum; 30 kDa isoform which probably results from differential glycosylation, 46 kDa disulfide-linked homodimer and 130 kDa heterodimer which is bound to the inactive form of the matrix metalloproteinase-9 (proMMP-9) (Bouchet and Bauvois, 2014).…”

Section: Introductionmentioning

confidence: 99%

Urine Neutrophil Gelatinase-Associated Lipocalin a Possible Diagnostic Marker for Egyptian Hepatocellular Carcinoma Patients

Abdelsameea

Nada

Omar

et al. 2020

Asian Pac J Cancer Prev

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Background: Most effective method for reducing mortality from hepatocellular carcinoma (HCC) is early diagnosis. Despite its lack of adequate sensitivity, ultrasound is considered fundamental for HCC screening. Aim: to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) as non-invasive marker for HCC diagnosis in Egyptian patients. Methods: One hundred and twenty patients were divided into three groups (40 patients each): patients with chronic viral hepatitis (HCV or HBV), cirrhotic patients and HCC patients and 40 healthy age and gender matched subjects were enrolled as control group. After clinical assessments, urinary NGAL was measured by enzyme-linked immunosorbent assay. Results: Our results revealed that median level of urinary NGAL was 290, 834, 1090 and 1925 pg/ml in control, chronic hepatitis, cirrhotic and HCC groups respectively among studied groups (p<0.001). Receiver operating characteristics (ROC) analysis showed that urinary NGAL cutoff value of 1255 ng/ml could discriminate between HCC and cirrhosis. The area under curve (AUC) was 0.95 with 90% sensitivity, 87.5% specificity (p-value <0.001). In HCC group, urine NGAL level didn`t show significant correlation with Child Pugh score, MELD score or Barcelona Clinic Liver Cancer (BCLC) stage. Conclusion: Urinary NGAL could be a simple, non-invasive test for diagnosis of HCC in chronic liver disease patients.

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Revisiting Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Cancer: Saint or Sinner?

Cited by 46 publications

References 86 publications

Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel

Therapeutic genome editing of triple-negative breast tumors using a noncationic and deformable nanolipogel

NGAL protects in nasopharyngeal carcinoma by inducing apoptosis and blocking epithelial‑mesenchymal transition

Urine Neutrophil Gelatinase-Associated Lipocalin a Possible Diagnostic Marker for Egyptian Hepatocellular Carcinoma Patients

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