Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 20, Pages -Publisher
MDPI
DOI: 10.3390/ijms222011018
Keywords
annexin A1; macrophage polarization; pancreatic cancer; extracellular vesicles; tumor microenvironment
Funding
- University of Salerno
- POR Campania, FESR 2014/2020 (Asse 1Obiettivo specifico 1.2Azione 1.2) Project: Campania OncoTerapie [CUP: B61G18000470007]
Ask authors/readers for more resources
The complex ANXA1/EVs in the TME of pancreatic cancer modulates macrophage polarization, further contributing to cancer progression, particularly by activating M2 macrophages to induce angiogenesis and matrix degradation.
The tumor microenvironment (TME) is a dynamic system where nontumor and cancer cells intercommunicate through soluble factors and extracellular vesicles (EVs). The TME in pancreatic cancer (PC) is critical for its aggressiveness and the annexin A1 (ANXA1) has been identified as one of the oncogenic elements. Previously, we demonstrated that the autocrine/paracrine activities of extracellular ANXA1 depend on its presence in EVs. Here, we show that the complex ANXA1/EVs modulates the macrophage polarization further contributing to cancer progression. The EVs isolated from wild type (WT) and ANXA1 knock-out MIA PaCa-2 cells have been administrated to THP-1 macrophages finding that ANXA1 is crucial for the acquisition of a protumor M2 phenotype. The M2 macrophages activate endothelial cells and fibroblasts to induce angiogenesis and matrix degradation, respectively. We have also found a significantly increased presence of M2 macrophage in mice tumor and liver metastasis sections previously obtained by orthotopic xenografts with WT cells. Taken together, our data interestingly suggest the relevance of ANXA1 as potential diagnostic/prognostic and/or therapeutic PC marker.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available