Antitumor effects of galectin-3 inhibition in human renal carcinoma cells

Abstract

Galectins are thought to be prognosticators for survival in renal cell cancer. However, the biological activity of galectin-3 (Gal-3) in renal carcinoma cells is still debated. In this study, immunohistochemical staining confirmed a high expression of Gal-3 in tumor tissue from renal cell carcinoma. Critically, Gal-3 expression was related to tumor cell differentiation. Consistent with Gal-3 expression in renal cell cancer, strong expression of Gal-3 was also observed in several renal tumor cell lines but not in normal renal cells. A Gal-3 high-expression cell line Caki-1 was chosen to study the biological activity of Gal-3. Using short hairpin RNA method, Gal-3 expression in Caki-1 cells was knocked down. We evidenced that Gal-3 knockdown inhibited cell proliferation and invasion, induced Caspase-3-dependent apoptosis and arrested cell cycle at G1 phase. Mechanically, Cyclin D1 expression decreased, but p27 increased after Gal-3 knockdown. Taken together, these results suggest that Gal-3 is related to the development of renal cell cancer and could serve as a target to therapy renal cell cancer.

Expression and Distribution of Galectin-3 in Chromophobe and Papillary Carcinomas

“…Gal-3 showed different patterns of expression including nuclear, cytoplasmic and membranous. Consistent with previous studies (19,20), cytoplasmic expression was the most common pattern identified in our cases and it was almost equally distributed between the histological subtypes (43% chromophobe carcinomas and 57% papillary carcinomas). By contrast, nuclear and membranous expressions were mainly identified in chromophobe tumors (70% and 70%, respectively).…”

“…In clear cell RCC tissues, Gal-3 was found to be strongly expressed compared to non-tumorous surrounding tissues, and its elevated levels were correlated with a poor prognosis (19,20,23,27). By contrast, a group of investigators reported that Gal-3 expression is lost during renal carcinogenesis, contributing to a reduced survival rate in patients with ccRCC (28).…”

“…A recent study reported that elevated levels of Gal-3 found in RCCs tissues at both mRNA and protein levels contribute to renal carcinogenesis, and concluded that this protein could be used as a therapeutic target for patients with conventional RCC (19). On the other hand, a high expression of Gal-3 was found in the chromophobe subtype compared to papillary one, and it has been put forward as a potential marker for the differential diagnosis of RCC (20).…”

Galectins and Carcinogenesis: Their Role in Head and Neck Carcinomas and Thyroid Carcinomas

“…Additionally, the mutation of gal-3 (serine 6 to alanine or glutamic acid) prevents phosphorylation, resulting in a decrease of its anti-apoptotic activity [ 51 ]. Furthermore, gal-3 has a role in cell proliferation, as the inhibition of this protein by knockdown lead to the decrease of esophageal and renal cancer cell proliferation in vitro [ 52 , 53 ]. In oral tongue squamous cell carcinoma, an in vitro study using Tca8113 cell line established that the overexpression of gal-3 increased cell proliferation.…”

Avaliação do papel de galectina-3 no recrutamento de macrófagos e sua participação na angiogênese em modelo de fibrossarcoma

“…Além de seu papel na adesão celular, gal-3 também promove a proliferação celular in vitro em muitos tipos de câncer, como de próstata (Wang et al, 2009), renal (Xu et al, 2016) e pancreático (Song et al, 2012). No entanto, a análise da expressão de PCNA e a contagem de figuras de mitose não apontaram diferenças no aspecto proliferativo entre tumores de animais WT e Gal-3 KO (FIGURAS 09 e 10).…”