title: Human glioblastoma tumours and neural cancer stem cells express the chemokine CX3CL1 and its receptor CX3CR1.
abstract: Human gliomas represent an unmet clinical challenge as nearly two-thirds of them are highly malignant lesions with fast progression, resistance to treatment and poor prognosis. The most severe form, the glioblastoma multiforme, is characterised by a marked and diffuse infiltration through the normal brain parenchyma. Given the multiple effects of chemokines on tumour progression, aim of this study was to analyse the expression of the chemokine CX3CL1 and of its specific receptor CX3CR1 in 36 human surgical glioma samples, with different degrees of histological malignancy and in glioblastoma-derived neurospheres. Herein we show that both ligand and receptor are expressed at the mRNA and protein levels in most specimens (31/36). While receptor expression was similarly detected in low or high grade tumours, the uppermost scores of CX3CL1 were found in grades III-IV tumours: oligodendrogliomas, anaplastic astrocytomas and glioblastomas. Accordingly, the expression of CX3CL1 was inversely correlated with patient overall survival (p = 0.01). Glioblastoma-derived neurospheres, containing a mixed population of stem and progenitor cells, were positive for both CX3CR1 and for the membrane-bound chemokine, which was further up-regulated and secreted after TNF-IFNγ stimulation. Confocal microscopy of 3D neurospheres showed that the ligand was primarily expressed in the outer layer cells, with points of co-localisation with CX3CR1, indicating that this ligand-receptor pair may have important intercellular adhesive functions. The high expression of CXC3L1 in the most severe forms of gliomas suggests the involvement of this chemokine and its receptor in the malignant behaviour of these tumours.
authors: Dept Immunology and Inflammation, IRCCS Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano, Milan, Italy.
authors: Marco
authors: M
authors: Erreni
authors: Graziella
authors: G
authors: Solinas
authors: Paola
authors: P
authors: Brescia
authors: Daniela
authors: D
authors: Osti
authors: Federica
authors: F
authors: Zunino
authors: Piergiuseppe
authors: P
authors: Colombo
authors: Annarita
authors: A
authors: Destro
authors: Massimo
authors: M
authors: Roncalli
authors: Alberto
authors: A
authors: Mantovani
authors: Riccardo
authors: R
authors: Draghi
authors: Daniel
authors: D
authors: Levi
authors: Riccardo
authors: R
authors: Rodriguez Y Baena
authors: Paolo
authors: P
authors: Gaetani
authors: Giuliana
authors: G
authors: Pelicci
authors: Paola
authors: P
authors: Allavena
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism*; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D023062:Receptors, Interleukin-8A / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D054428:Chemokine CX3CL1; D009363:Neoplasm Proteins; D023062:Receptors, Interleukin-8A