Table 1.
Agents targeting LCN2 and possible LCN2-associated pathways affecting breast cancer metastasis
| Agents | Breast cancer lines or mouse models | Mechanisms | References |
|---|---|---|---|
| Anti-mLCN2 antibody | Nude mice implanted with 4T1 cells | Destabilizes LCN2/MMP-9 complex | Leng et al 200959 |
| NFAT3 | ERA+ breast cancer: MCF-7, T-47D, ZR-75-1 and BT-474 | NFAT3/LCN2 axis controls motility | Fougère et al 201067 |
| C/EBPζ | TNBC: MDA-MB-231 | Represses LCN2 gene promoter activity and MMPs | Wang et al 201168 |
| Trastuzumab | HER2-positive SKBr3 | Inhibits LCN2 via the PI3K/AKT pathway | Kumandan et al 201369 |
| HIC1 | TNBC: MDA-MB-231 and MDA-MB-468 | Inhibits LCN2 secretion by the AKT pathway, reducing cell migration and invasion | Cheng et al 201431 |
| CXCR4 with LCN2 siRNA | TNBC: MDA-MB-436 and MDA-MB-231 | Inhibits CXCR4 and LCN2 pathways simultaneously | Guo et al 201470 |
| ICAM-Lcn2-LP | TNBC: MDA-MB-231 | LCN2 knockdown reduces VEGF and angiogenesis | Guo et al 201644 |
| MART-10 | TNBC: MDA-MB-231 MDA-MB-453 | Suppresses LCN2, decreasing MMP-9 activity and cell migration and invasion | Chiang et al 201671 |
Abbreviations: AKT, protein kinase B; C/EBPζ, CCAAT enhancer-binding protein; CXCR4, C–X–C chemokine receptor type 4; ERA+, estrogen receptor α-positive; HIC1, hypermethylated in cancer 1; ICAM-Lcn2-LP, intercellular adhesion molecule-1-targeted, Lcn2 siRNA-encapsulating liposome; LCN2, lipocalin 2; MART-10, 19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3; MMP-9, matrix metalloproteinase-9; NFAT3, nuclear factor of activated T-cells 3; PI3K, phosphotylinosital-3-kinase; TNBC, triple-negative breast cancer; VEGF, vascular endothelial growth factor.