Review Looks at Role Lipocalin 2 Might Play in Spread of Breast Cancer

A recent review looked at the role lipocalin 2 (LCN2), a secreted glycoprotein that transports small lipophilic ligands, might play in metastatic triple-negative breast cancer (TNBC) and the possibility of potential LCN2-targeting agents.

TNBC is a very aggressive cancer with a poor prognosis. There are no targeted therapies approved, leaving only chemotherapy as an option most of the time.

Lipocalins are part of a group of more than 20 diverse proteins that exhibit limited amino acid sequence similarity.

LCN2 acts as an initiator of carcinogenesis and metastasis through multiple signaling pathways, and it has gained attention as a potential biomarker and a modulator of human cancer. Due to its property as a secretory protein, LCN2 can be easily detected in the blood or urine, and could be a noninvasive diagnostic and prognostic biomarker for breast cancer progression, the authors wrote.

Abnormal expression of LCN2 has been assigned critical roles in various pathologies, including inflammation, renal damage, liver injury, and cancer in several human organs. In breast cancer, the abnormal expression of LCN2 serves critical roles in the epithelial-to-mesenchymal transition (EMT) process, angiogenesis, and cell migration and invasion.

As a result, high LCN2 expression is an independent prognostic biomarker for reduced survival among patients with breast cancer, especially for those suffering from TNBC.

EMT is a developmental process that is typically activated during cancer invasion and metastasis. LCN2 can upregulate mesenchymal markers, including vimentin and fibronectin, and downregulate the epithelial marker E-cadherin, which induces EMT and significantly increases cell motility and invasion

A recent study identified that LCN2 is a regulator of angiogenesis, and the downregulation of TNBC-secreted LCN2 is associated with suppressed tumor angiogenesis in breast cancer, making it a potential anti-angiogenic target in TNBC. As a result, LCN2 silencing in aggressive breast cancer cells can inhibit cell migration and the mesenchymal phenotype.

The authors wrote that it is it is important to identify a potential LCN2-targeted therapeutic approach for the prevention and treatment of TNBC, concluding that since LCN2 promotes local tumor invasion and cancer metastasis by inducing EMT and stimulating angiogenesis in vitro and in vivo, it suggests that LCN2 may be a promising therapeutic target in inhibiting breast cancer progression.

Reference

Hu C, Yang K, Li M, Huang W, Zhang F, Wang H. Lipocalin 2: a potential therapeutic target for breast cancer metastasis. [published online November 16, 2018]. Onco Targets Ther. doi: 10.2147/OTT.S181223.