Expression and Functions of Galectin-7 in Human and Murine Melanomas (original) (raw)
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Role of galectin-3 in tumour metastasis
Moscow University Chemistry Bulletin, 2010
We used metastatic variant of B16 melanoma (B16F1) to study lung colonization galectin-3-deficient (gal-3−/−) C57BL/6 mice. In vivo study showed that compared with gal-3+/+ mice, gal-3−/−mice exhibited resistance to lung colonization of B16F1 melanoma cells (p +/+ mice (p −/− suggesting that galectin-3 is considered as therapeutic target.
A distinctive role for galectin-7 in cancer ?
Frontiers in Bioscience, 2012
Introduction 3. Galectin-7: Comparison with other members of the galectin family 3.1. Galectins 3.2. Distinctive expression pattern of galectin-7 3.3. Cellular localization of galectin-7 4. Galectin-7 in cancer 4.1. The pro-apoptotic function of galectin-7: a logical role in suppressing tumor growth 4.2. Unexpected roles of galectin-7 4.3. Galectin-7: a marker for mammary myoepithelial cells and aggressive breast cancer? 5. Other functions for galectin-7 6. Concluding remarks 7. Acknowledgement 8. References
The American Journal of Pathology, 2006
The immune system recognizes diverse melanoma antigens. However , tumors can evade the immune response , therefore growing and progressing. It has been reported that galectin-3 and galectin-1 can induce apoptosis of activated lymphocytes. However , there is strong evidence indicating that the regulation of galectins function in the human tumor microenvironment is a complex process that is influenced by diverse biological circumstances. Here , we have investigated 33 biopsies (eight primary and 25 metastases) from 24 melanoma patients (15-72 years old) and describe the correlation between the expression of galectin-3 or galectin-1 and the level of apoptosis of tumor-associated lymphocytes using immunohistochemistry and an in situ nick translation assay. The range of galectin-3-positive tumor cells varied between 0% and 93% and that of galectin-1-positive tumor cells varied between 5% and 97%. In addition, 23 ؎ 27% of tumor-associated lymphocytes were apoptotic. Although our results show a correlation between galectin-3 expression and apoptosis of tumorassociated lymphocytes, we could not find such correlation with galectin-1. Considering the complex process of cancer immunoediting, various interacting factors must be considered.
Galectin-3 expression favors metastasis in murine melanoma
Galectin-3 is a member of the lectin family that binds β-galactosides and plays an important role in several types of tumors. Melanoma is an invasive cancer responsible for 80% of deaths associated to skin cancers. There are some evidences that galectin-3 interacts with β-catenin, a molecule involved with Wnt signal-ing pathway. Here, we evaluate the role of galectin-3 in tumor growth and metastasis, as well as its interaction with β-catenin. Murine melanoma cells (B16F10) were injected subcutaneously and intravenously in male C57BL/6 wild-type (WT) and galectin-3 knockout (KO) mice. Tumor growth and lung melanoma colonies were assessed. The expression of galectin-3 and β-catenin was evaluated by immuno-histochem-istry. We observed that tumor growth did not differ between the groups. However, to metastasis, the number of lung colonies in WT mice was significantly increased in comparison to that observed in KO mice. The cytoplasm expression of galectin-3 was observed in subcutaneous and metastatic tumors, in both groups. We observed its nuclear expression in some of subcu-taneous tumors of KO mice. The expression of β-cate-nin was detected in cell membrane of all subcutane-ous tumors analyzed, whereas in the metastatic tumors we observed both cytoplasm and cell membrane staining. Altogether, our data suggest that galectin-3 favors the metastasis of melanoma cells and this process is not associated with β-catenin.
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.
Archives of Dermatological Research, 2005
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.
Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention
Tumor Biology
Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, par...
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.
Galectin-1 in Melanoma Biology and Related Neo-Angiogenesis Processes
Journal of Investigative Dermatology, 2012
Aggressiveness of advanced melanomas relates in part to their marked propensity to develop neoangiogenesis and metastases. Among its numerous pro-cancer roles, galectin (gal)-1 expressed and/or secreted by both cancer and endothelial cells stimulates proliferation and angiogenesis. This study first shows that gal-1 is more highly expressed at both mRNA and protein levels than its congeners in melanomas and particularly in advanced lesions. The roles of gal-1 were further investigated in vivo in the highly proliferating and vascularized pseudometastatic B16F10 mouse melanoma model using stable knockdown B16F10 cells and wild-type versus gal-1 knockout mice, and then in vitro in B16F10 tumoral and lung microvascular cells. Gal-1 depletion in the B16F10 tumor cells but not in the tumor-bearing mice significantly increased melanoma-bearing mice survival. Tumor-derived gal-1 thus seems to have more critical roles than the host-derived one. In fact, gal-1 displays distinct effects on the H-Ras-dependent p53/p21 pathways: in primary lung microvessel endothelial cells, gal-1 seems to be involved in the maintenance of senescent status through the induction of both p53 and p21 while it stimulates B16F10 cancer cell proliferation through a p53/p21 decrease. Altogether, these data point to gal-1 as a potential target to combat melanomas.