Loxl2-flox Mouse

Loxl2, or Lysyl Oxidase Like 2, belongs to the lysyl oxidase (LOX) family. It is a copper and lysine tyrosyl-quinone (LTQ)-dependent amine oxidase. Its canonical function is to catalyze the cross-linking of elastin and collagen in the extracellular matrix (ECM), which is crucial for maintaining tissue integrity. It is involved in various biological processes and is associated with multiple diseases, especially cancer [1,2]. Genetically modified mouse models have been instrumental in exploring its in vivo role [1].

In pancreatic ductal adenocarcinoma (PDAC) mouse models, Loxl2 ablation had little impact on primary tumor development but significantly decreased metastasis and increased overall survival, attributed to non-cell autonomous factors like ECM remodelling. Conversely, Loxl2 overexpression promoted primary and metastatic tumor growth and decreased survival, linked to increased epithelial-mesenchymal transition (EMT) and stemness. Tumor-associated macrophage-secreted oncostatin M (OSM) was identified as an inducer of Loxl2 expression [3].

In conclusion, Loxl2 plays a significant role in ECM remodelling. Gene knockout and overexpression mouse models in PDAC have revealed its dual role in primary tumor growth, metastasis, and overall survival. These findings highlight its potential as a therapeutic target in treating metastatic PDAC and other related diseases where ECM remodelling and EMT play crucial roles.