Lipocalin 2 could predict circulating MMP9 levels in patients with breast cancer

Bahrun, Uleng; Wildana, Wildana; Rahmawati, Hegaria; Kurniawan, Liong Boy; Hamdani, William

doi:10.3233/bd-219017

Cited by 3 publications

(1 citation statement)

References 10 publications

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“…MMPs, well-known metalloproteases are involved in invasion and matrix degradation. MMP9, one of the metalloprotease has also been shown to form complex with LCN2, which further stabilizes MMP9 and its activity 46 . HeLa cells upon treatment with anti-LCN2 antibody, showed a reduction in the expression of active metalloproteases in gelatine zymography experiment, suggesting a quick degradation of these proteases and thus inhibiting migratory and invasive ability of HeLa cells (figure 2e).…”

Section: Anti-lcn2 Antibody Abrogates the Tumorigenicity Of Cervical ...mentioning

confidence: 99%

In vitroandin vivoevidences propound therapeutic potential of Lipocalin 2 in cervical carcinoma

Dwivedi

Mazumder

Veeraraghavan

et al. 2023

Preprint

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Cervical cancer (CC), the second most common in developing countries and the third most common in developed nations, is the fourth most common type of cancer in women overall. The HPV16 high-risk genotype of the virus, which is responsible for about 61% of cervical cancer incidences, was found to have higher LCN2 levels in advanced clinical CC stages. In this study, we assessed the impact of suppressing LCN2 activity after treatment with an anti-LCN2 monoclonal antibody (MAb) in both in vitro and in vivo settings. Anti-LCN2 antibody was found to reduce proliferation and invasion of HeLa cells, the first immortal cells from a HPV positive aggressive adenocarcinoma of the cervix. LCN2 and its ligand MMP9 was found to be highly expressed in the cells and abrogated on treatment with anti-LCN2. The five receptors of LCN2 - SLC22A17, MC1R, MC2R, MC4R and LRP2 were barely detected with or without treatment. Anti-LCN2 Mab caused tumors to regress and soften in vivo, in a xenograft mouse model. Analysis of histology images of the treated and untreated tumor established the necrotic capability of the therapeutic molecule explaining the regression and softening of the tumor. Differential gene expression analysis between untreated and treated tumor proved that LCN2 inhibition abolished the migratory, invasive, and hypoxic pathways while significantly increasing the necrosis and cell death pathways in tumor after treatment with the monoclonal antibody. LCN2 inhibition was shown molecularly to lead to tumor regression via a negative feedback loop of LCN2 through the TNFα-IL17 axis exponentially increasing the effect of the anti-LCN2 monoclonal antibody. In conclusion, LCN2 appears to be a viable therapeutic target, and the monoclonal antibody used in this study can be further developed for clinical usage in cervical cancer.

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Section: Anti-lcn2 Antibody Abrogates the Tumorigenicity Of Cervical ...mentioning

confidence: 99%

In vitroandin vivoevidences propound therapeutic potential of Lipocalin 2 in cervical carcinoma

Dwivedi

Mazumder

Veeraraghavan

et al. 2023

Preprint

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CRISPR/Cas9-mediated knockout of Lcn2 in human breast cancer cell line MDA-MB-231 ameliorates erastin-mediated ferroptosis and increases cisplatin vulnerability

et al. 2022

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Lipocalin-2 promotes breast cancer brain metastasis by enhancing tumor invasion and modulating brain microenvironment

Zhao,

Tang,

Lei

et al. 2024

Front. Oncol.

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Breast cancer is the leading cancer diagnosed in women globally, with brain metastasis emerging as a major cause of death, particularly in human epidermal growth factor receptor 2 positive and triple-negative breast cancer subtypes. Comprehensive understanding of the molecular foundations of central nervous system metastases is imperative for the evolution of efficacious treatment strategies. Lipocalin-2 (LCN2), a secreted iron transport protein with multiple functions, has been linked to the progression of breast cancer brain metastasis (BCBM). In primary tumors, LCN2 promotes the proliferation and angiogenesis of breast cancer cells, triggers the epithelial-mesenchymal transition, interacts with matrix metalloproteinase-9, thereby facilitating the reorganization of the extracellular matrix and enhancing cancer cell invasion and migration. In brain microenvironment, LCN2 undermines the blood-brain barrier and facilitates tumor seeding in the brain by modulating the behavior of key cellular components. In summary, this review meticulously examines the fuel role of LCN2 in BCBM cascade, and investigates the potential mechanisms involved. It highlights the potential of LCN2 as both a therapeutic target and biomarker, indicating that interventions targeting LCN2 may offer improved outcomes for patients afflicted with BCBM.

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Lipocalin 2 could predict circulating MMP9 levels in patients with breast cancer

Cited by 3 publications

References 10 publications

In vitroandin vivoevidences propound therapeutic potential of Lipocalin 2 in cervical carcinoma

In vitroandin vivoevidences propound therapeutic potential of Lipocalin 2 in cervical carcinoma

CRISPR/Cas9-mediated knockout of Lcn2 in human breast cancer cell line MDA-MB-231 ameliorates erastin-mediated ferroptosis and increases cisplatin vulnerability

Lipocalin-2 promotes breast cancer brain metastasis by enhancing tumor invasion and modulating brain microenvironment

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