Galectins Are Differentially Expressed in Supratentorial Pilocytic Astrocytomas, Astrocytomas, Anaplastic Astrocytomas and Glioblastomas, and Significantly Modulate Tumor Astrocyte Migration

Abstract

Galectins, a family of mammalian lectins with specificity to ␤-galactosides, are involved in growthregulatory mechanisms and cell adhesion. A relationship is assumed to exist between the levels of expression of galectins and the level of malignancy in human gliomas. A comparative study of this aspect in the same series of clinical samples is required to prove this hypothesis. Using computerassisted microscopy, we quantitatively characterized by immunohistochemistry the levels of expression of galectins-1, -3 and -8 in 116 human astrocytic tumors of grades I to IV. Extent of transcription of galectins-1, -3, and -8 genes was investigated in 8 human glioblastoma cell lines by means of RT-PCR techniques. Three of these cell lines were grafted into the brains of nude mice in order to characterize in vivo the galectins-1, -3 and -8 expression in relation to the patterns of the tumor invasion of the brain. The role of galectin-1, -3 and -8 in tumor astrocyte migration was quantitatively determined in vitro by means of computer-assisted phase-contrast videomicroscopy. The data indicate that the levels of galectin-1 and galectin-3 expression significantly change during the progression of malignancy in human astrocytic tumors, while that of galectin-8 remains unchanged. These three galectins are involved in tumor astrocyte invasion of the brain parenchyma since their levels of expression are higher in the invasive parts of xenografted glioblastomas than in their less invasive parts. Galectin-3, galectin-1, and to a lesser extent galectin-8, markedly stimulate glioblastoma cell migration in vitro. Since bands for the transcripts of human galectins-2, -4 and -9 were apparently less frequent and intense in the 8 human glioblastoma cell lines, this system provides an excellent model to assign defined roles to individual galectins and delineate overlapping and distinct functional aspects.

SPARC upregulates MT1-MMP expression, MMP-2 activation, and the secretion and cleavage of galectin-3 in U87MG glioma cells

“…We previously reported [5] that galectin-3 expression increases during glioma progression, whereas other studies have found a global decrease in expression [7,14]. This discrepancy may be due to the specific regions of tumors analyzed, as higher galectin-3 expression is associated with the invasive regions in vivo.…”

“…This discrepancy may be due to the specific regions of tumors analyzed, as higher galectin-3 expression is associated with the invasive regions in vivo. Indeed, glioblastoma cells demonstrated greater motility on galectin-3 in vitro, suggesting that increased galectin-3 promotes invasion [7]. In addition, galectin-3 expression is not restricted to the tumor cells.…”

Nuclear galectin-3 expression is an independent predictive factor of recurrence for adenocarcinoma and squamous cell carcinoma of the lung

“…18 The specificity of the galectin-3 antibody was checked by immunoblotting and ELISA assays with controls to exclude any crossreactivity to other galectins (especially galectin-1, which is abundant in human lungs), as previously detailed. [18][19][20]33 An internal positive control consisted in the expression of galectin-3 (also labeled Mac-2) by alveolar macrophages. The negative control sections were immunostained under the same conditions, but with the omission of the primary antibody.…”

“…15,16 Galectins are involved in cell growth, apoptosis and cell migration features. [17][18][19][20] Of these 14 galectins, galectin-3, a chimera-type galectin, is of special interest since its structure harbors a sugar-combining site, a collagensensitive stalk and a short N-terminated section, acting as a target for phosphorylation. 21 What is particularly intriguing about this sole chimera-type galectin is its presence in nuclear, cytoplasmic and extracellular sites, 22 its ability to interact with a variety of carbohydrate and protein ligands and to form pentamers with unique crosslinking abilities, 23 its strong antiapoptotic activity coupled with the nuclear export of the phosphorylated form (for example in chemotherapeutic treatment), 24 and its effect on promoter activity of cyclin D1, 25 which is a prognostic marker in the adenocarcinoma subgroup of lung carcinomas.…”

Binding Affinities of Carbohydrate-Conjugated Chlorins for Galectin-3

“…12 It acts as a physiological modulator of cellular adhesion and growth and may be involved in neoplastic transformation. [13][14][15] Like galectin-3, galectin-8 is approximately 80% homologous in amino acid sequence between human and mouse. 11 The expression of galectin-3 has recently emerged as a potential diagnostic marker of some cancers.…”