A distinctive role for galectin-7 in cancer ? (original) (raw)
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Varied expression and localization of multiple galectins in different cancer cell lines
Oncology Reports, 2008
Galectins play a key role in oncogenic processes. Although several galectins are known, their relative expression at the mRNA and protein levels, the subcellular localization, and their relationship to the oncogenic manifestation remains unclear. Herein we report a comprehensive characterization of the expression of major galectins in human breast cancer (drug-sensitive MCF-7 and drug-resistant MCF-7/Adr R), colon cancer (HCT-116 and HT-29), and glioma (T98G) cell lines, as these cells are common model systems for studying oncogenic processes. The expected ~14.5 kDa galectin-1, predominantly cytosolic, was detected in the cancer and normal cell lines. Notably, two different molecular forms of galectin-1 with molecular masses of ~13.5 and 15 kDa were detected in T98G cells, the latter being in the extracellular medium, perhaps a result of post-translational processing. Immunocytochemistry indicated that the extracellular galectin-1 bound to the cell surface was punctated in appearance, suggesting that it was bound to specific receptors. Immunohistological studies indicated that metastasizing carcinomas express high levels of galectin-1. On the other hand, galectin-3 was readily detectable in all cancer cell lines but undetectable in normal cell lines, indicating that galectin-3 is a cancer-specific biomarker protein. Galectin-3 was a cytosolic protein but was not detected in the extracellular medium, indicating that cancer cells do not secrete this galectin. Finally, despite the RT-PCR analysis suggesting the presence of two transcripts of galectin-8 in all cancer cell lines, the corresponding ~36 kDa protein was only detectable in the nuclear and cytosolic fractions upon cell fractionation. Notably, a different molecular form of galectin-8 of ~18 kDa was immunoprecipitated from the extracellular media, suggesting that the secreted galectin-8 undergoes post-translational processing. These results highlight the expression of galectins in different molecular forms in cancers, warranting caution in interpreting the results of functional studies of individual galectins, particularly because these proteins function redundantly in cancer pathways.
Alterations in Galectin-3 Expression and Distribution Correlate with Breast Cancer Progression
The American Journal of Pathology, 2004
To define the role of galectin-3 in breast cancer progression, we have used a novel three-dimensional co-culture system that recapitulates in vivo reciprocal functional breast epithelial-endothelial cell-cell and cell-matrix interactions, and examined the expression of galectin-3 mRNA and protein in human breast tumors and xenografts. Galectin-3 is required for the stabilization of epithelial-endothelial interaction networks because immunoneutralization with galectin-3 antibodies abolishes the interactions in a dose-dependent manner. Co-culture of epithelial cells with endothelial cells results in increase in levels of secreted galectin-3 and presence of proteolytically processed form of galectin-3 in the conditioned media. In contrast, intracellular galectin-3 predominantly exists in the intact form. This difference in sensitivity to proteolytic processing of secreted versus intracellular galectin-3 probably arises from differences in accessibility of protease-sensitive sites, levels, and/or type of activated protease(s), and may be indicative of different functional roles for intact and processed galectin-3. To determine whether the proteolytically cleaved galectin-3 retains its ability to bind to endothelial cells, binding assays were performed with the full-length and matrix metallopeoteinase-2-cleaved recombinant galectin-3. Although a dose-dependent increase in binding to human umbilical vein endothelial cells was observed with both full-length and cleaved galectin-3, proteolytically cleaved galectin-3 displayed ϳ20-fold higher affinity for human umbili-
Down-Regulation of Galectin-3 Suppresses Tumorigenicity of Human Breast Carcinoma Cells
Clinical Cancer Research, 2001
Galectin-3 is an endogenous -galactoside-binding protein with specificity for type I and II ABH blood group epitopes and poly-N-acetyllactosamine glycan-containing cell surface glycoproteins and is the major nonintegrin cellular laminin-binding protein. Galectin-3 is expressed at an elevated level in a wide range of neoplasms, and expression was shown to be associated in some tumor cell systems with metastases. Here we determined the functional consequence of blocking galectin-3 expression in highly malignant human breast carcinoma MDA-MB-435 cells. Inhibition of galectin-3 expression led to reversion of the transformed phenotype as determined by altered morphology, loss of serumindependent growth, acquisition of growth inhibition properties by cell contact, and abrogation of anchorageindependent growth. The blockage of galectin-3 expression led to a significant suppression of tumor growth in nude mice. These results provide direct evidence that galectin-3 expression is necessary for the maintenance of the transformed and tumorigenic phenotype of MDA-MB-435 breast carcinoma cells. The abbreviation used is: rgalectin-3, recombinant galectin-3; FBS, fetal bovine serum; MFP, mammary fat pad. Downloaded from a Cells were injected into the MFP region of nude mice as described in "Materials and Methods." b Number of tumors/number of animals.
The American Journal of Pathology, 2010
Galectins are members of a family of -galactosidesbinding proteins that have recently emerged as novel modulators in different aspects of cancer. The expression of galectins in tumors and/or the tissue surrounding them has been well documented. Since galectin-7 expression has been associated with epithelial tissues and varies significantly in various types of cancer , we have investigated for the first time its role in breast cancer. Using two preclinical mouse models , high levels of galectin-7 expression in breast cancer cells drastically increased their ability to metastasize to lungs and bones. Significant increases in the number of pulmonary metastases and osteolytic lesions were induced by overexpression of galectin-7 compared with control cells. In human tissues , galectin-7 was specifically found in myoepithelial cells of normal human breast tissue , but not in luminal cells. Its expression was severely altered in breast carcinoma , many samples showing greater than 70% of galectin-7 positive cells. High expression levels of galectin-7 were restricted to high-grade breast carcinomas , including HER2 overexpressing and basal-like groups. In HER2 overexpressing cases , galectin-7 expression was associated with lymph node axillary metastasis. Taken together , our results indicate that galectin-7 may represent a potential target for both specific detection and therapeutic inhibition of metastatic breast cancer.
Expression and functions of galectin-7 in ovarian cancer
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Glycobiology, 2010
Galectin-3 is a glycan-binding protein that mediates cell-cell and/or cell-extracellular matrix (ECM) interactions. Although galectin-3 is implicated in the progression of various types of cancers, the mechanisms by which galectin-3 enhances metastasis remain unclear. In order to elucidate the role of galectin-3 in the complex multistage process of cancer metastasis, we examined galectin-3 and galectin-3-binding sites expression in a series of 82 spontaneous canine mammary tumours (CMT) and two CMT cell lines. Benign CMT tumours exhibited strong nuclear/cytoplasmic galectin-3 immunostaining whereas malignant CMT tumours and metastases exhibited dramatically decreased galectin-3 expression with the majority of the immunostaining confined to the cytoplasm. Curiously, intravascular tumour cells overexpressed galectin-3 regardless of their location. Malignant CMT cell line (CMT-U27) generated xenografts with the same pattern of galectin-3 expression found in malignant CMT. In parallel with the downregulation of galectin-3, malignant CMT displayed an overall loss of galectin-3-binding sites in the ECM and focal expression of galectin-3-binding sites mainly detected in intravascular tumour cells and endothelium. Furthermore, loss of galectin-3-binding sites was correlated with the downregulation of GLT25D1, a β (1-O) galactosyltransferase that modifies collagen, and upregulation of stromal galectin-1. Finally, GLT25D1 mRNA expression was strikingly downregulated in malignant CMT-U27 compared to the benign cell line and its expression was further decreased in galectin-3 knockdown CMT-U27 cell line. We hypothesized that the loss of galectin-3-binding sites in the ECM in conjunction with the overexpression of galectin-3 in specific tumour cell subpopulations are important events for the development of mammary tumour metastases.
Galectins dysregulation: A way for cancer cells to invade and pervade
Oncology Research
Galectins are sticky molecules that bind to β-galactoside. Their interactions render them essential players in many cellular processes. The imbalance of galectin expression was reported in many diseases. In cancer, galectins interact with the extracellular matrix, evade the immune system, and potentially have broad interactions with blood components. In the last ten years, since 2010, we did focus on galectin research in different cancer types. Our findings showed an interaction between cancer cells and erythrocytes via galectin-4. Moreover, we found that upregulation of galectins was associated with lymph node metastasis in ovarian cancers. Hence, with this, we shortly review some important aspects of galectins and their potential importance in more profound understanding of cancer progression and the field of cancer biomarkers. Galectins are Potentially Supporting Cancer Cells to Invade and Metastasize via Interaction with Blood Components In 2017, an interaction between cancer cells and erythrocytes was reported and interpreted by galectin-4 interaction with the blood group antigen (Fig. 1). Displacement of galectin-4 to attachment points of cancer cells and erythrocytes was noticed. Also, we found in this article, a co-localization of galectin-4 and blood group antigen was seen using double fluorescent immunostaining. Moreover, a morphological deformation of red blood cells was seen to be associated with this interaction [1]. In this model, interacting cells were dividing without the presence of an attachment surface. In addition, developing lamellipodia/filopodia was noticed after interactions [1]. According to the structure of galectins, all surface/secreted galectins might interact with erythrocytes. Thus, many questions have been raised regarding the dysregulation of galectins in cancer. For instance, is the upregulation of galectins related to invasive cancers or lymph node metastasis? Thus, our group sought mRNA expression in many types of cancers, including AML [2,3], ovarian [4], endometrial, and breast (unpublished). Consistent with our hypothesis, in ovarian cancer, we found that galectin-9 might be a potential marker for lymph node metastasis [4]. Supportive Biological Evidence and Functions Related to Galectins and Cancer Galectin family Galectins are protein family that have a high affinity for binding to β-galactoside like N-acetyllactosamine via Nlinked or O-linked glycosylation. Galectins are a structurally associated family containing at least one carbohydrate recognition domain (CRD) [5,6]. The CRD of this family is folded into a β-sandwich structure consisting of two stretched antiparallel β-sheets. Galectin's ligand binds to the groove formed by β-sandwich [7]. Up to now, there are sixteen members of the galectins family. Depending on their structure, galectins are categorized into three different types: prototype, tandem repeat or chimera. Prototypical galectins (LGALS1, 2, 5, 7, 10, 11, 13, 14 and 15) contain one CRD that can dimerize. Tandem galectins (LGALS4, 6, 8, 9, and 12) are at least two CRD linked together by a small peptide domain. Galecin-3 is the only member that contains one CRD linked to the N-terminal non-lectin domain [8,9]. These structural aspects render them a key players in several cellular processes, as shown in Fig. 2. Subcellular localization Galectins display a wide range of distribution (Table 1
Molecular Biology Reports, 2021
Purpose Galectin-3 is a M r 31,000 protein that belongs to a family of carbohydrate-binding proteins. Galectin-3 has already been associated with protection against apoptosis through cell to cell or cell to matrix adhesion processes. It seems that galectin-3 plays an important role in tumor progression, cell growth, invasion and metastasis. Galectin-3 is the only member of the chimeric galectins that has an N-terminal glycine and proline domain and a C-terminal carbohydrate recognition domain that allows galectin-3 to accommodate larger structures such us polylactosaminoglycans and intervene to DNA damage repair process. In this systematic review, our primary goal is to identify the effect of galectin-3 expression in association with drug resistance and apoptosis inhibition in breast cancer. Materials and methods Scopus and PubMed databases were searched on 26 November 2018 using the following combination of keywords: (galectin-3 OR gal-3 OR LGALS3) AND (breast cancer) AND (chemoresistance OR (drug resistance) OR chemosensitivity). All the articles in English, regardless the time of publication, text availability and species included were initially accepted. Results In the majority of the included studies, the expression of galectin-3 had a protective role in cell survival via different pathways such as the response to DNA damage and repair or the inhibition of apoptosis after treatment with a chemotherapeutic agent. Conclusion Galectin-3 expression in breast tumors might be an important factor in the selection of the most suitable treatment.
Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 2020
PURPOSE Galectin-1 is a lectin involved in the carcinogenesis of many cancers. In the present study, we aimed to investigate the importance of galectin-1 in breast cancer carcinogenesis and its relationship with tumor development. METHODS Patients who were diagnosed with new breast cancer and a healthy volunteer population were included in the study. Preoperative and postoperative (1 month following visit at the medical oncology outpatient clinic) serum samples were collected from breast cancer patients and the healthy volunteer control group. RESULTS There was no statistically significant difference between patients' age, height, weight and body mass index (BMI) (p>0.05). The mean galectin-1 value of the preoperative group was 2.16±0.69 ng/ml, in the postoperative group; 1.75±0.31 ng/ml, and the healthy control group 1.64±0.40 ng/ml. A comparison of mean galectin-1 values between the groups showed that the highest galectin-1 level was found in the preoperative patients. When...
Galectin-1, -3 and -9 Expression and Clinical Significance in Squamous Cervical Cancer
PLOS ONE, 2015
Galectins are proteins that bind β-galactoside sugars and provide a new type of potential biomarkers and therapeutic targets in cancer. Galectin-1,-3 and-9 have become the focus of different research groups, but their expression and function in cervical cancer is still unclear. The aim of this study was to determine the phenotype of galectin-1,-3 and-9 expressing cells and the association with clinico-pathological parameters in cervical cancer. Galectin expression was scored in tumor cells, tumor epithelium infiltrating immune cells and stromal cells in squamous cervical cancer (n = 160). Correlations with clinico-pathological parameters and survival were studied according to the REMARK recommendations. We additionally investigated whether the galectins were expressed by tumor cells, fibroblasts, macrophages and T cells. Galectin-1 and-9 were both expressed by tumor cells in 11% of samples, while 84% expressed galectin-3. Strong galectin-1 expression by tumor cells was an independent predictor for poor survival (hazard ratio: 8.02, p = 0.001) and correlated with increased tumor invasion (p = 0.032) and receiving post-operative radiotherapy (p = 0.020). Weak and positive tumor cell galectin-3 expression were correlated with increased and decreased tumor invasion, respectively (p = 0.012). Tumor cell expression of galectin-9 showed a trend toward improved survival (p = 0.087). The predominant immune cell type expressing galectin-1,-3 and-9 were CD163 + macrophages. Galectin-1 and-3 were expressed by a minor population of T cells. Galectin-1 was mainly expressed by fibroblasts in the tumor stroma. To conclude, while tumor cell expression of galectin-9 seemed to represent a beneficial response, galectin-1 expression might be used as a marker for a more aggressive anti-cancer treatment.