Annexin A1 May Induce Pancreatic Cancer Progression as a Key Player of Extracellular Vesicles Effects as Evidenced in the In Vitro MIA PaCa-2 Model System.

Abstract	Pancreatic Cancer (PC) is one of the most aggressive malignancies worldwide. As annexin A1 (ANXA1) is implicated in the establishment of tumour metastasis, the role of the protein in PC progression as a component of extracellular vesicles (EVs) has been investigated. EVs were isolated from wild type (WT) and ANXA1 knock-out (KO) PC cells and then characterised by multiple approaches including Western blotting, Field Emission-Scanning Electron Microscopy, and Dynamic Light Scattering. The effects of ANXA1 on tumour aggressiveness were investigated by Wound-Healing and invasion assays and microscopic analysis of the Epithelial to Mesenchymal Transition (EMT). The role of ANXA1 on angiogenesis was also examined in endothelial cells, using similar approaches. We found that WT cells released more EVs enriched in exosomes than those from cells lacking ANXA1. Notably, ANXA1 KO cells recovered their metastatic potential only when treated by WT EVs as they underwent EMT and a significant increase of motility. Similarly, human umbilical vein endothelial cells (HUVEC) migrated and invaded more rapidly when treated by WT EVs whereas ANXA1 KO EVs weakly induced angiogenesis. This study suggests that EVs-related ANXA1 is able to promote cell migration, invasion, and angiogenesis, confirming the relevance of this protein in PC progression.
Authors	Emanuela Pessolano, Raffaella Belvedere, Valentina Bizzarro, Paola Franco, Iolanda De Marco, Amalia Porta, Alessandra Tosco, Luca Parente, Mauro Perretti, Antonello Petrella
Journal	International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 12 (Dec 04 2018) ISSN: 1422-0067 [Electronic] Switzerland
PMID	30518142 (Publication Type: Journal Article)
Chemical References	Annexin A1
Topics	Annexin A1 (metabolism) Cell Line, Tumor Cell Movement Disease Progression Endothelial Cells (metabolism) Epithelial-Mesenchymal Transition Extracellular Vesicles (metabolism) Gene Knockout Techniques Human Umbilical Vein Endothelial Cells (metabolism) Humans Models, Biological Neoplasm Invasiveness Pancreatic Neoplasms (metabolism, pathology) Phenotype

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