Increased Galectin-3 Expression in Gastric Cancer: Correlations with Histopathological Subtypes, Galactosylated Antigens and Tumor Cell Proliferation

Abstract

Galectin-3 represents an endogenous galactoside-binding lectin which may be involved in tumor cell adhesion and proliferation. In order to evaluate its biological significance in human gastric cancer, we investigated its expression in the stomach of a large series of patients (n = 193) by immunohistochemical staining with the monoclonal antibody Mac-2. Compared to normal tissues, primary gastric adenocarcinomas showed a slight increase in galectin-3 expression. However, there was no correlation of membrane-bound and cytoplasmic galectin-3 with histopathological differentiation parameters (according to the WHO and Laurén classifications) or tumor progression (as documented by pTNM staging). Nuclear galectin-3 reactivity was significantly stronger in diffuse-type cancer compared to the intestinal-type tumors. Galectin-3 binds to terminal GalNAcα(1–3) bound to polylactosamine chains and related glycotopes. Therefore, the strong coexpression of membrane/cytoplasmic galectin-3 with Griffonia simplicifolia agglutinin I (GSA I) binding sites (Galα1–3Gal-, GalNAcα–) on carcinoma cells seems to be interesting. On the other hand, nuclear galectin-3 immunoreactivity did not correlate with the incidence of Ki-67-positive tumor cells. A prognostic value of galectin-3 regarding patient survival could not be established.

Proteomic analysis of isolated membrane fractions from superinvasive cancer cells

“…Furthermore, studies of RPMI-2650 variants suggest that galectin-3 expression correlates with nasal carcinoma cell invasiveness [22]. Using the monoclonal antibody M3/38 that was raised against glycoprotein extracts, increased expression of Galectin-3 was observed in cancers from thyroid [23], central nervous system [24], head and neck squamous cell carcinoma [25], pancreas [26], bladder [27], stomach [28] and renal carcinoma [29].…”

Extracellular galectin-3 counteracts adhesion and exhibits chemoattraction in Helicobacter pylori-infected gastric cancer cells

“…The localization and subcellular expression was shown to be dependent on the tissue, cell type, proliferative state and level of differentiation (Okada et al, 2006). An increase in Gal-3 expression is linked to increased malignancy in gastric adenocarcinomas and in a number of tumours (Baldus et al, 2000;Miyazaki et al, 2002). Interestingly, Gal-3 is upregulated and rapidly secreted as a host response to H. pylori infection (Fowler et al, 2006).…”

Gene deregulation in gastric cancer

“…Absence of RUNX3 expression and promoter hypermethylation has also been detected in human colorectal cancer and lung cancer (Ku et al, 2004;Li et al, 2004). In gastric cancerespecially in peritoneal metastases -overexpression of Galectin-3 (LGALS3) has been observed (Baldus et al, 2000;Sakakura et al, 2002). This may be a consequence of deregulated RUNX3 expression: in skeletal tissues gene expression of Galectin-3 is regulated by RUNX2 .…”