Galectin-3 expression in gliomas according to its distinct molecular domains: a tissue microarrays study

Abstract

Galectins are carbohydrate binding proteins, represented by fifteen members phylogenetically conserved L-lectins found in multicellular organisms, from yeast to mammals. Among the different types of galectins, Galectin - 3 (Gal- 3) is highlighted due to its role in tumorigenesis, tumor progression and dissemination, and survival of neoplastic cells. We described, together with other researchers, Gal- 3 as a potential biomarker in gliomas. Since it has become differentially expressed in the astrocytic tumors according to their different degrees of malignancy, evaluation of the expression of Gal- 3 was found to be useful in distinguishing between pilocytic astrocytoma (grade I) and diffuse astrocytomas (grade II) as well as anaplastic oligodendrogliomas (grade III) and glioblastomas (GBMs). We observed that the expression of Gal-3 in GBMs is not homogeneous, i.e., there is a greater expression of this lectin in neoplastic cells, primarily at the cytoplasmic level, around areas of necrosis, cellular pseudopalisades - whose biological significance has not yet fully clarified. One hypothesis is that the GBM cells of pseudopalisades are more resistant to apoptosis and are in process of cell migration. On the other hand, there are several conflicting results in the literature about the expression of Gal-3 diffuse gliomas, most possibly due to different clones of antibodies and immunohistochemical protocols. Thus, it becomes necessary a systematic and meticulous comparison of Gal-3 immunostaining in diffuse gliomas using antibodies aimed to different Gal-3 regions (the C-terminal, N-terminal and transmembrane regions). In this project, we propose to evaluate the expression of Gal-3 by immunohistochemistry in a series of GBMs, anaplastic oligodendrogliomas, pilocytic astrocytomas and even in ependymomas through tissue microarrays (TMAs) using antibodies aimed to distinct epitopes of Gal-3. We intend to perform simultaneous evaluation of the expression of Gal-3 and markers of cellular proliferation and cell migration, resistance to apoptosis through double-labeling approach. Therefore, we intend to continue the line of research on Gal-3 in gliomas, providing a throughout investigation of this biomarker that has been established as useful tool in the differential diagnosis between some types of gliomas. Because Gal-3 is a carbohydrate binding protein and a transducer molecule for cell signaling, this lectin is potential therapeutic target. Finally, the concomitant evaluation of the expression of this lectin with other cellular markers will allow us even more information and insights about the possible role of Gal-3 in diffuse gliomas. (AU)