title: Melanoma cells homing to the brain: an in vitro model.
abstract: We developed an in vitro contact through-feet blood brain barrier (BBB) model built using type IV collagen, rat astrocytes, and human umbilical vein endothelial cells (HUVECs) cocultured through Transwell porous polycarbonate membrane. The contact between astrocytes and HUVECs was demonstrated by electron microscopy: astrocytes endfeet pass through the 8.0 μm pores inducing HUVECs to assume a cerebral phenotype. Using this model we evaluated transmigration of melanoma cells from two different patients (M1 and M2) selected among seven melanoma primary cultures. M2 cells showed a statistically significant higher capability to pass across the in vitro BBB model, compared to M1. Expression of adhesion molecules was evaluated by flow cytometry: a statistically significant increased expression of MCAM, αvβ3, and CD49b was detected in M1. PCR array data showed that M2 had a higher expression of several matrix metalloproteinase proteins (MMPs) compared to M1. Specifically, data suggest that MMP2 and MMP9 could be directly involved in BBB permeability and that brain invasion by melanoma cells could be related to the overexpression of many MMPs. Future studies will be necessary to deepen the mechanisms of central nervous system invasion.
authors.affiliation: Laboratory of Clinical Pathology and Medical Genetics, Foundation IRCCS Neurological Institute Carlo Besta, Via Celoria 11, 20133 Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rizzo
authors.affiliation: Laboratory of Clinical Pathology and Medical Genetics, Foundation IRCCS Neurological Institute Carlo Besta, Via Celoria 11, 20133 Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Vasco
authors.affiliation: Laboratory of Clinical Pathology and Medical Genetics, Foundation IRCCS Neurological Institute Carlo Besta, Via Celoria 11, 20133 Milano, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Girgenti
authors.affiliation: U.O. Neuropathology, IRCCS Foundation C. Besta Neurological Institute, Foundation IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milano, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Fugnanesi
authors.affiliation: U.O. Neuropathology, IRCCS Foundation C. Besta Neurological Institute, Foundation IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milano, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Calatozzolo
authors.affiliation: Cellular Neurobiology Laboratory, Cerebrovascular Diseases Unit, Foundation IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milano, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Canazza
authors.affiliation: Neurologia-Stroke Unit, Manzoni Hospital, Via dell'Eremo 9/11, 23900 Lecco, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Salmaggi
authors.affiliation: Unit of Immunotherapy, Fondazione IRCCS National Cancer Institute, Via Venezian 1, 20133 Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Rivoltini
authors.affiliation: U.O. Neuropathology, IRCCS Foundation C. Besta Neurological Institute, Foundation IRCCS Neurological Institute C. Besta, Via Celoria 11, 20133 Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Morbin
authors.affiliation: Laboratory of Clinical Pathology and Medical Genetics, Foundation IRCCS Neurological Institute Carlo Besta, Via Celoria 11, 20133 Milano, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ciusani
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D009363:Neoplasm Proteins