Expression of galectin-3 in primary and metastatic melanoma: immunohistochemical studies on human lesions and nude mice xenograft tumors

Abstract

Galectins are a large family of proteins which bind galactoside-containing glycans. Their role in cancer seems to be important since members of the family may mediate cell adhesion and modulate cell growth. Galectin-3 (Gal-3) is expressed in the nucleus, in the cytoplasm and on the cell surface, and can also be secreted into the extracellular matrix. A series of experimental and clinical data have been reported which indicate that Gal-3 may play a putative role in carcinogenesis, cancer progression and the process of metastasis. To study the possible correlation between Gal-3 expression and malignant potential in primary melanoma lesions, we conducted an immunohistochemical study with monoclonal anti-Gal-3 antibody in a series of primary and metastatic melanoma lesions as well as benign skin pigmented lesions. We also developed a xenograft melanoma model in nude mice with two melanoma cell lines (ATCC G-361 and ATCC HT-144) and assessed staining with the Gal-3 antibody in the xenografts and the metastases. The expression of anti-Gal-3 staining was determined semiquantitatively. The expression of Gal-3 was higher in thin primary melanoma lesions than in benign pigmented skin lesions or metastases and seemed to correlate inversely with the aggressiveness as estimated by the Breslow index which is recognized as the main prognostic factor in melanoma. We propose Gal-3 expression in melanoma as a diagnostic and/or a prognostic parameter and suggest that further studies of such a role for Gal-3 are warranted.

Different expression of lysosome-associated membrane protein-1 in human melanomas and benign melanocytic lesions

“…Sarafian et al [39] suggested that LAMP proteins might serve as ligands for cell adhesion molecules and demonstrated in vitro a positive correlation between enhanced galectin-3 binding to LAMP-expressing cells and an increase in the expression of both LAMP-1 and LAMP-2 proteins. On the other hand, however, it was recently demonstrated that the expression of galectin-3 is strong in primary melanomas and drops significantly in more advanced lesions and in melanoma metastases [40]. The results from our study taken together with observations of [40] contradict the results of in-vitro studies by Sarafian et al [39].…”

Galectin-3 expression favors metastasis in murine melanoma

“…Here, we have demonstrated the involvement of galectin-3 in murine melanoma growth and metastases. We observed prominent expression of galectin-3 in B16F10 cells, a finding that has also been described in other studies dealing with human and murine melanoma cell lines [29,30]. A similar result has previously indicated that the overexpression of galectin-3 may confer a selective survival advantage and a resistance to apoptosis in human breast carcinoma cell lines by specifically in- Figure 3.…”

“…Thick tumors exhibited weak intensity, whereas thin tumors manifested intermediate staining intensity. The same finding was observed in a study using a melanoma cell line in a mouse experimental model [30]. However, in half of the knock-out animals, galectin-3 expression was observed in both cytoplasm and nucleus.…”

“…Therefore, our results seem to reflect this crucial phase that prepares the cell to initiate Wnt signaling upon melanoma progression. Some studies have indicated a relationship between galectin-3 and Wnt/ catenin, such as a recent report demonstrating that galectin-3 expression in the cytoplasm and nucleus of welldifferentiated thyroid neoplasms seems to be associated with the activation of the Wnt signaling pathway, suggesting a role for galectin-3 in thyroid carcinogenesis [30].…”

Decreased Immunoreactive Maspin Expression in Intermediate Thickness and Thick Primary Melanoma Lesions

“…The slides were counterstained using The extent of immunohistochemical staining was estimated by determining a global score, which was calculated by adding the proportion and intensity scores together to produce a total (Σ). 22 haematoxylin (Dako S2020). A haematoxylin-stained histological control slide, which was not exposed to primary antibody, was obtained for each specimen to act as a negative control.…”