The Role of Adhesion Molecules and Extracellular Vesicles in an In Vitro Model of the Blood–Brain Barrier for Metastatic Disease

Author:

Vasco Chiara1ORCID,Rizzo Ambra1ORCID,Cordiglieri Chiara23ORCID,Corsini Elena1ORCID,Maderna Emanuela4ORCID,Ciusani Emilio1ORCID,Salmaggi Andrea5

Affiliation:

1. Laboratory of Clinical Chemistry SMeL122, Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, Italy

2. Preclinical Neuroimmunology Lab, Neurology IV Fondazione IRCCS Istituto Neurologico “Carlo Besta”, 20133 Milan, Italy

3. Imaging Facility, National Institute of Molucular Genetics (INGM) “Romeo ed Enrica Invernizzi”, c/o Policlinico di Milano Hospital, Padiglione Invernizzi, Via Francesco Sforza 35, 20122 Milan, Italy

4. Neurology 5/Neuropathology Unit, Fondazione IRCCS Istituto Neurologico C. Besta, 20133 Milan, Italy

5. Neuroscience Department-Neurology/Stroke Unit, Ospedale A. Manzoni, ASST Lecco, 23900 Lecco, Italy

Abstract

Metastatic brain disease (MBD) has seen major advances in clinical management, focal radiation therapy approaches and knowledge of biological factors leading to improved prognosis. Extracellular vesicles (EVs) have been found to play a role in tumor cross-talk with the target organ, contributing to the formation of a premetastatic niche. Human lung and breast cancer cell lines were characterized for adhesion molecule expression and used to evaluate their migration ability in an in vitro model. Conditioned culture media and isolated EVs, characterized by super resolution and electron microscopy, were tested to evaluate their pro-apoptotic properties on human umbilical vein endothelial cells (HUVECs) and human cerebral microvascular endothelial cells (HCMEC/D3) by annexin V binding assay. Our data showed a direct correlation between expression of ICAM1, ICAM2, β3-integrin and α2-integrin and the ability to firmly adhere to the blood–brain barrier (BBB) model, whereas the same molecules were down-regulated at a later step. Extracellular vesicles released by tumor cell lines were shown to be able to induce apoptosis in HUVEC while brain endothelial cells showed to be more resistant.

Funder

Italian Ministry of Health

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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