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.