Galectin-1 had previously been shown to be elevated in a variety of cancers such as head and neck squamous cell carcinoma, thyroid cancer or hepatocellular carcinoma
[13, 14, 21]. Moreover, the plasma levels of galectin-1 were shown to be significantly higher in RCC patients when compared to healthy controls
. Galectin-3 had also previously been associated with several cancer entities, such as small-cell lung cancer, gastric and colorectal cancer
[22–24]. Previous studies were able to show an up-regulation of galectin-3 in RCC
It is well known that the expression of galectin variants varies between different organ tissues
. Therefore we took great interest in identifying the relative galectin-1 and galectin-3 mRNA concentration by using tumor and non-tumor tissue from the same patient as reference. By doing so, we were able to eliminate any intra individual variance in distribution of galectin-1 and -3.
In contrast to our findings, previous studies implicated a possible negative correlation of galectins with regard to RCC cancer
. Albeit, these results were based on immunohistochemistry of proteins and not on mRNA expression analysis, they show that the physiological role of galectins is highly complicated and may vary between subtypes. Additionally, among the tumor samples of the aforementioned study a high expression of galectin-3 was initially noted that vanished with increasing stage and grade among tumors and therefore showed the reported results.
In the present study a significantly increased expression of galectin-1 and galectin-3 mRNA in RCC was shown when compared to normal adjacent renal tissue.
These findings support the hypothesis that galectin-1 and -3 may play a role in RCC progression or carcinogenesis. In this study extend of disease and lymph node involvement did not correlate with galectin-1 or galectin-3 mRNA expression.
Significance levels were narrowly missed. Others could show a significant correlation of advanced RCC and metastasis for galectin-3 using real time PCR as well as immunehistochemistry
Our findings of higher galectin-1 and -3 levels in clear cell RCC tissue of male patients and the fact that neither of the two encoding genes is located on the sex chromosomes is very interesting since RCC most predominantly occurs in the male population.
With regard to a possible mechanism of action, previous data on various tumors suggest that galectin-3 may mediate invasion and the migration of cancer cells via the Wnt/ β-catenin signaling pathway and Akt (Protein Kinase B) phosphorylation. The proposed model describes galectin-3 to increase Akt phosphorylation, thereby increasing phosphorylation and inactivation of glycogen synthase kinase-3 β (GSK-3 β). With inactivation of GSK-3 β, the degradation of β-catenin is reduced. With increased cellular levels, β-Catenin can translocate to the nucleus and activate transcription after binding to transcription factors
[30, 31]. Others have argued that the effect of galectins in the immune T-cell response plays an important role: Higher levels of galectin-3 for instance have previously been shown to induce T-cell apoptosis, thereby providing a potential immune escape mechanism
. The latter findings originate from animal models, colorectal cancer research or in vitro studies. The impact of galectin mediated T-cell supression had not yet been fully shown in RCC
Our findings are not without limitations. One possible issue in our evaluation might be a possible contamination of renal cell tissue with lymphocytes. Lymphatic cells are often predominantly found in or around cancerous tissue. It has been shown that the expression of galectins is upregulated in the presence of stimulated B-cells where they play a putative role in immune modulation and T-cell control
. Likewise immune mediated activation of T-cells is known to lead to an increased expression of galectin-1
. In view of our histopathological control sections we can however exclude higher concentrations of lymphatic tissue invasion. Therefore the aforementioned confounding effects may not play an important role in this study. In addition, our data are in accordance with other studies showing equivalent elevations of galectins in cancerous tissue
[26, 29, 37, 38].
Our data on galectin-1 and -3 encourage further investigations such as the influence on survival in larger patient cohorts or the relevance of these proteins with regard to new therapeutic agents and targeted therapy. Further studies should also include the role of galectin-1 and -3 on the protein level as well as sex specific expression.