Loxl2, or Lysyl Oxidase Like 2, is a copper and lysine tyrosyl-quinone (LTQ)-dependent amine oxidase belonging to the lysyl oxidase (LOX) family. Its canonical function is to catalyze the cross-linking of elastin and collagen in the extracellular matrix (ECM) [2]. It is involved in multiple biological processes, and its dysregulation is associated with various diseases [1-8]. Genetically modified mouse models with silenced or overexpressed Loxl2 have enabled in-depth exploration of its in vivo role [1].

In pancreatic ductal adenocarcinoma (PDAC), Loxl2 ablation in mouse models (KPCL2KO or KCL2KO) had little effect on primary tumour development but significantly decreased metastasis and increased overall survival, mainly through non-cell autonomous factors like ECM remodelling. Conversely, Loxl2 overexpression (KPCL2KI or KCL2KI) promoted primary and metastatic tumour growth and decreased overall survival, linked to increased epithelial-mesenchymal transition (EMT) and stemness. Tumour-associated macrophage-secreted oncostatin M (OSM) was identified as an inducer of Loxl2 expression [3].

In conclusion, Loxl2 plays a crucial role in regulating ECM cross-linking. Model-based research, especially using Loxl2 KO mouse models in PDAC, has revealed its significant role in tumour metastasis and overall survival, highlighting its potential as a therapeutic target in cancer treatment.