# Lipocalin-2 in Triple-Negative Breast Cancer: A Review of Its Pathophysiological Role in the Metastatic Cascade

**Authors:** Diandra T. Keller, Ralf Weiskirchen, Sarah K. Schröder-Lange

PMC · DOI: 10.3390/ijms262210938 · International Journal of Molecular Sciences · 2025-11-12

## TL;DR

This paper reviews how Lipocalin-2 contributes to the spread of triple-negative breast cancer and its potential as a prognostic marker.

## Contribution

The paper provides a comprehensive review of LCN2's role in TNBC metastasis, highlighting its tumor-promoting functions and potential clinical relevance.

## Key findings

- LCN2 is associated with poor prognosis in triple-negative breast cancer and contributes to metastasis.
- LCN2 influences tumor processes like angiogenesis and therapy resistance.
- LCN2 may drive metastasis to specific organs like the lung and brain.

## Abstract

Lipocalin-2 (LCN2) is a 25 kDa glycoprotein that has been shown to be a multifunctional player in the metastasis of triple-negative breast cancer (TNBC). In physiological contexts, LCN2 exhibits bacteriostatic properties and plays key roles in iron homeostasis and the transport of hydrophobic molecules. However, several studies have shown that aberrant LCN2 expression is associated with poor prognosis in various malignancies, including breast cancer, which is the most common cancer in women worldwide and can be classified into four molecular subtypes. Among these, TNBC represents a disproportionately aggressive subtype characterized by poor prognosis and high metastatic potential. Although LCN2 has been extensively studied in breast cancer overall, its specific role in TNBC progression and metastasis is only beginning to be understood. Recent evidence suggests that LCN2 contributes to several tumor-promoting processes such as angiogenesis, therapy resistance and modulation of the tumor microenvironment. Moreover, LCN2 appears to influence organ-specific metastasis, particularly to the lung and brain, while its role in liver and bone dissemination remains unclear. Collectively, current data identify LCN2 as a critical mediator of TNBC progression and highlight its potential as a prognostic factor and modulator of disease progression. This review aims to summarize insights from both in vitro and in vivo studies, with particular focus on the role of LCN2 in the metastatic cascade, while also addressing existing research gaps and critically evaluating the current findings.

## Linked entities

- **Genes:** LCN2 (lipocalin 2) [NCBI Gene 3934]
- **Diseases:** triple-negative breast cancer (MONDO:0005494), breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}
- **Diseases:** breast cancer (MESH:D001943), TNBC (MESH:D064726), cancer (MESH:D009369), metastasis (MESH:D009362)
- **Chemicals:** iron (MESH:D007501)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

151 references — full list in the complete paper: https://tomesphere.com/paper/PMC12652116/full.md

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Source: https://tomesphere.com/paper/PMC12652116