Correlation of galectin-3/galectin-3-binding sites with low differentiation status in head and neck squamous cell carcinomas☆☆☆

Abstract

The accurate determination of levels of differentiation is of prognostic value in human head and neck squamous cell carcinomas (HNSCCs). Because the deliberate selection of biochemical determinants accompanying certain stages of differentiation can refine the predictive power of histochemical assessments, the application of the quantitative evaluation of staining distribution and intensity by computer-assisted microscopy is one prerequisite to potential improvements. We used 2 innovative approaches with peanut agglutinin based on encouraging results with respect to common lectin-histochemistry. First, we used a custom-made neoglycoprotein to monitor the presence of Thomsen-Friedenreich (T) antigen-binding sites. Second, we measured the presence of 2 galectins immunohistochemically and, at the same time, measured lectin-histochemically the presence of accessible ligands for the endogenous lectins. We also monitored the presence of calcyclin, a protein with relevance to cell cycle progression or exocytosis. With 61 cases of HNSCC as their basis, including 31 oral, 20 laryngeal, and 10 hypopharyngeal lesions, the data show that the main modifications observed in connection with a loss of differentiation are related to a modification in the levels of both galectin-3/galectin-3-binding site and T-antigen/T-antigen-binding site expressions. The data obtained also suggest that galectin-3 could act as an acceptor site for the T antigen. Because the level of differentiation is known to be indicative of the recurrence rate in HNSCCs and our data clearly indicate that galectin-3 and the T antigen (and their respective binding sites) are involved in dedifferentiation processes, further investigation is warranted into the roles of galectins in HNSCC tumor progression and recurrence analysis.

Differentiation-Dependent Glycosylation of Cells in Squamous Cell Epithelia Detected by a Mammalian Lectin

“…Bar = 10 Ìm. edly differentiated parts of carcinomas in contrast to the presence of ligands for galectin-1 in these systems [Delorge et al, 2000;Plzá k et al, 2000]. The suprabasal expression of Gal-3-binding sites, observed in the studied human and pig epithelia, corroborates these observations and is suggestive of potential auto-and/or paracrine functions of this galectin.…”

“…Gal-3 expression was detected predominantly in suprabasal layers of squamous cell epithelia, while its presence is very sparse or lacking in the basal cell layer and in cells of basal cell cancer of skin [Konstantinov et al, 1994;Holíková et al, 1999;. Using labeled Gal-3 as probe, highly differentiated cells of squamous cell carcinomas are positive in contrast to cells with a low level of differentiation [Delorge et al, 2000;Plzá k et al, 2000]. In this system, galectin-1-binding proved to be less selective [Plzá k et al, 2000].…”

Comprehensive galectin fingerprinting in a panel of 61 human tumor cell lines by RT-PCR and its implications for diagnostic and therapeutic procedures

“…Engineered ligand derivatives are instrumental in delineating such alterations in the architecture of the combining sites (Solõ s et al 1996;RuÈ diger et al 2000). Histochemically, these dierences have begun to be exploited in tumor diagnosis by the introduction of labeled galectins as tools in pathology (Andre et al 1999;FrancË ois et al 1999;Schwarz et al 1999;Delorge et al 2000;Plza k et al 2000).…”

Galectin-1 and galectin-3 in fetal development of bovine respiratory and digestive tracts

“…Together with observations on the spatiotemporal appearance of these two proteins in the reproductive tracts of pregnant mice and the murine hair cycle (Phillips et al 1996;Wollina et al 2000), it can be concluded that their expression is most probably under differential control in developing and mature organs. Remarkably, when assessed in tumor tissue, this characteristic harbors diagnostic value (Schwarz et al 1999;Delorge et al 2000). Two different routes of investigation will now be taken to continue to unravel the relevance of galectins in tissue development and homeostasis.…”