Glycoconjugate Journal 20, 227–238, 2004 C  2004 Kluwer Academic Publishers. Manufactured in The Netherlands. REVIEW Tumor galectinology: Insights into the complex network of a family of endogenous lectins Harald Lahm 1 , Sabine Andr ´ e 2 , Andreas Hoeflich 3 , Herbert Kaltner 2 , Hans-Christian Siebert 2 , Bernard Sordat 4 , Claus-Wilhelm von der Lieth 5 , Eckhard Wolf 3 and Hans-Joachim Gabius 2 1 Immunology-Molecular Biology Laboratory (IML), Thoraxklinik Heidelberg gGmbH, Amalienstrasse 5, D-69126 Heidelberg, 2 Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University, Veterin¨ arstrasse 13, D-80539 M¨ unchen, 3 Institute of Molecular Animal Breeding, Gene Center, Ludwig-Maximilians-University, Feodor-Lynen-Strasse 25,D-81377 M¨ unchen, 4 Experimental Pathology Unit, Swiss Institute for Experimental Cancer Research (ISREC), Chemin des Boveresses 155, CH-1066 Epalinges, 5 Central Spectroscopic Division, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg β-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 consid- ered 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 con- cept 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 biolog- ical 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. Published in 2004. Keywords: apoptosis, galectin, invasion, metastasis, tumor diagnosis, tumor marker Introduction The cell surface displays a variety of determinants which are relevant for the cells’ communication with the environment and their social behavior. Alterations in the profile of cell surface epitopes are thus likely to reflect shifts in cellular parameters To whom correspondence should be addressed: PD Dr. Harald Lahm, Immunology-Molecular Biology Laboratory (IML), Thoraxklinik Heidelberg gGmbH, Amalienstrasse 5, D-69126 Heidelberg. Tel.: +49-6221-396 647; Fax: +49-6221-396 622; E-mail: harald.lahm@ thoraxklinik-heidelberg.de such as differentiation and malignancy. An illustrative example for the way how malignant transformation impinges on prop- erties of the cells’ exterior surface has been given by analyzing the carbohydrate chains of cellular glycoconjugates. This pro- cedure to map the complete set of glycan structures (glycome) is currently referred to as glycomic profiling. Disease develop- ment and progression is often associated with changes in the glycome [1–14]. Monoclonal antibodies and plant/invertebrate lectins are instrumental to detect and localize deviations from the glycosylation patterns of normal cells [15–19]. While it has become straightforward to detect plant-lectin-reactive