LOXL2 in pancreatic tumourigenesis: the complexity of tumour–stromal crosstalk exemplified
Menée in vitro et à l'aide de modèles murins d'adénocarcinome canalaire du pancréas, cette étude met en évidence un mécanisme par lequel les macrophages associés à la tumeur favorisent la croissance tumorale et le processus métastatique via la sécrétion d'oncostatine M et l'expression de la protéine LOXL2
The role of the lysyl oxidase (LOX) family of enzymes, consisting of LOX and LOX-like (LOXL) proteins 1–4, is to catalyse the crosslinking of collagen and elastin in the extracellular matrix (ECM). Members of the family have been implicated in tumour progression in a range of cancers, with multiple studies suggesting that LOX/LOXL-mediated ECM remodelling facilitates tumour cell invasion and metastasis. Increased expression, particularly of LOX and LOXL2, has been noted in many aggressive cancers and has been linked to reduced survival. However, the mechanisms of action are still unclear, and there is an ongoing debate over whether expression is tumour supporting or tumour suppressive.1 2 This appears, to some degree at least, to be dependent on tumour site, stage and even the source of expression, highlighting the need to understand the cell and stage-specific consequences of LOX/LOXL activity.Pancreatic ductal adenocarcinoma (PDAC) is notable for the abundance of collagen in the tumour microenvironment (TME), and as such has been the focus of several studies examining LOX or LOXL2 activity. However, the conflicting results reported have raised as many questions as answers. Indeed, more generally, there has been controversy over the stroma and ECM in PDAC, and although they clearly influence disease initiation and aggressiveness, they can exhibit tumour-suppressive activity in some contexts.3 In this issue, Alonso-Nocelo et al sought to address some of these questions, investigating the role of LOXL2 in pancreatic tumourigenesis using model systems.4The authors exploited genetically engineered mouse models of loss or gain of LOXL2 expression …
Gut , commentaire, 2021