Tumor galectinology: Insights into the complex network of a family of endogenous lectins

Abstract

Beta-Galactosides of cell surface glycoconjugates are docking sites for endogenous lectins of the galectin family. In cancer cells, primarily galectins-1 and -3 have been studied to date. With the emergence of insights into their role in growth control, resistance to or induction of apoptosis and invasive behavior the notion is supported that they can be considered as functional tumor markers. In principle, the same might hold true for the other members of the galectin family. But their expression in tumors has hitherto been a subject of attention only to a very limited extent. Pursuing our concept to define the complexity of the galectin network in cancer cells and the degree of functional overlap/divergence with diagnostic/therapeutic implications, we have introduced comprehensive RT-PCR monitoring to map their galectin gene expression. The data on so far less appreciated galectins in this context such as galectins-4 and -8 vindicate this approach. They, too, attach value to extend the immunohistochemical panel accordingly. Our initial histopathological and cell biological studies, for example on colon cancer progression, prove the merit of this procedure. Aside from the detection of gene expression profiles by RT-PCR, the detailed molecular biological monitoring yielded further important information. We describe different levels of regulation of galectin production in colon cancer cells in the cases of the tandem-repeat-type galectins-8 and -9. Isoforms for them are present with insertions into the peptide linker sequence attributed to alternative splicing. Furthermore, variants with distinct amino acid substitutions (galectin-8, Po66-CBP, PCTA-1, CocaI/II and galectin-9/ecalectin) and generation of multiple mRNA species, notably those coding for truncated galectin-8 and -9 versions with only one lectin site, justify to portray these two family members not as distinct individuals but as groups. In aggregate, the ongoing work to thoroughly chart the galectin network and to disentangle the individual functional contributions is expected to make its mark on our understanding of the malignant phenotype in certain tumor types.

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

“…Gal-8 is one of the most widely expressed galectins in human tissues (Hadari et al, 1995;Bidon et al, 2001) and is also common in cancerous cells (Bidon-Wagner and Le Pennec 2004;Lahm et al, 2004). In the immune system Gal-8 can play important roles in the homeostasis of T- Tribulatti et al, 2007;Norambuena et al, 2009;Tribulatti et al, 2009;Tribulatti et al, 2012) and B-cells (Tsai et al, 2011).…”

Varied expression and localization of multiple galectins in different cancer cell lines

“…Numerous ligands for galectin-1 have been described in different tissues and cells that include actin, laminin, fibronectin, vitronectin, integrins, CA-125, H-ras, CD45 and gemin-4 (6,(12)(13)(14)(15). Galectin-1 is expressed in a variety of cell types including breast epithelial, thymic epithelial, endothelial and dendritic cells, macrophages, fibroblasts and bone marrow cells (2,(16)(17)(18)(19)(20). There is an increased galectin-1 expression in many cancer types including colon, breast, ovary and prostate carcinomas and aggressive gliomas, and an increased accumulation of galectin-1 in the stroma surrounding tumors in ovarian and prostate carcinoma (2,(21)(22)(23)(24)(25).…”

“…Galectin-1 is expressed in a variety of cell types including breast epithelial, thymic epithelial, endothelial and dendritic cells, macrophages, fibroblasts and bone marrow cells (2,(16)(17)(18)(19)(20). There is an increased galectin-1 expression in many cancer types including colon, breast, ovary and prostate carcinomas and aggressive gliomas, and an increased accumulation of galectin-1 in the stroma surrounding tumors in ovarian and prostate carcinoma (2,(21)(22)(23)(24)(25). Other galectins, specifically galectin-3 and -8, are involved in a variety of cellular and carcinogenic processes similar to galectin-1.…”

Identification of Early Intestinal Neoplasia Protein Biomarkers Using Laser Capture Microdissection and MALDI MS

“…LGALS2 belongs to the galectin family that binds specifically to ␤-galactose-containing oligosaccharides (49). Although LGALS2 has not been previously reported as overexpressed in intestinal neoplasia, galectin-1 and galectin-3, two other proteins in the galectin family, have been shown to be up-regulated in human colon cancer (50), pancreatic cancer (51), and head and neck squamous cell carcinoma (52).…”