Deregulated expression of Elastin Microfibril Interfacer 2 (EMILIN2) in gastric cancer affects tumor growth and angiogenesis

Eva Andreuzzi; Albina Fejza; Alessandra Capuano; Evelina Poletto; Eliana Pivetta; Roberto Doliana; Rosanna Pellicani; Andrea Favero; Stefania Maiero; Mara Fornasarig; Renato Cannizzaro; Renato V Iozzo; Paola Spessotto; Maurizio Mongiat

doi:10.1016/j.mbplus.2020.100029

Deregulated expression of Elastin Microfibril Interfacer 2 (EMILIN2) in gastric cancer affects tumor growth and angiogenesis

Matrix Biol Plus. 2020 Feb 19:6-7:100029. doi: 10.1016/j.mbplus.2020.100029. eCollection 2020 May.

Affiliations

¹ Department of Research and Diagnosis, Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Italy.
² Department of Clinical Oncology, Experimental Gastrointestinal, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Italy.
³ Department of Pathology, Anatomy, and Cell Biology and the Cancer Cell Biology and Signaling Program, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.

Abstract

Gastric cancer is a frequent human tumor and often a lethal disease. Targeted therapy for gastric carcinomas is far behind vis-à-vis other solid tumors, primarily because of the paucity of cancer-driving mutations that could be efficiently and specifically targeted by current therapy. Thus, there is a need to discover actionable pathways/proteins and new diagnostic and prognostic biomarkers. In this study, we explored the role of the extracellular matrix glycoprotein EMILIN2, Elastin Microfibril Interfacer 2, in a cohort of gastric cancer patients. We discovered that EMILIN2 expression was consistently suppressed in gastric cancer and high expression levels of this glycoprotein were linked to abnormal vascular density. Furthermore, we found that EMILIN2 had a dual effect on gastric carcinoma cells: on one hand, it decreased tumor cell proliferation by triggering apoptosis, and on the other hand, it evoked the production of a number of cytokines involved in angiogenesis and inflammation, such as IL-8. Collectively, our findings posit EMILIN2 as an important onco-regulator exerting pleiotropic effects on the gastric cancer microenvironment.

Keywords: 5-FU, 5-fluorouracil; Angiogenesis; CAFCA, Centrifugal Assay for Fluorescence-based Cell Adhesion; CD31, cluster of differentiation 31 also known as PECAM-1; ECM, extracellular matrix; EGFR, epidermalgrowth factor receptor; EMILIN 2, Elastin Microfibril Interfacer 2; Extracellular matrix; GC, gastric cancer; Gastric cancer; HER2, human epidermal growth factor receptor 2; IGFBP2, insulin growth factor-binding protein 2; Inflammation; PFS, progression free survival; Serpin 1, serine protease inhibitor 1; Tumor microenvironment; VEGFA, vascular endothelial growth factor A.