Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor

Nagy, Nathalie; Bronckart, Yves; Camby, Isabelle; Legendre, Hugues; Lahm, Harald; Kaltner, Herbert; Hadari, Yaron R.; Ham, Philippe Van; Yeaton, Paul; Pector, Jean Claude; Zick, Yehiel; Salmon, Isabelle; Danguy, André; Kiss, Róbert; Gabius, Hans‐Joachim

doi:10.1136/gut.50.3.392

Cited by 113 publications

(100 citation statements)

References 44 publications

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“…This indicates that tumor cells may make significant contributions to the increased circulation of those galectin members. On the other hand, cellular expressions of galectin-8 and -4 have been reported to be lower in colorectal cancer than in healthy colonic epithelium (29,30). It seems likely, therefore, that other cells, for example, stromal or immune cells, may be the major contributor to the Ã , P < 0.05; ÃÃ , P < 0.01; ÃÃÃ , P < 0.001.…”

Section: Discussionmentioning

confidence: 82%

Serum Galectin-2, -4, and -8 Are Greatly Increased in Colon and Breast Cancer Patients and Promote Cancer Cell Adhesion to Blood Vascular Endothelium

Barrow

Guo

Wandall

et al. 2011

Clinical Cancer Research

146

136

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Purpose: Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells to vascular endothelium in vitro and experimental metastasis in vivo. This study determined the levels of galectin-1, -2, -3, -4, -8, and -9 in the sera of healthy people and patients with colon and breast cancer and assessed the influence of these galectins on cancer-endothelium adhesion.Experimental Design: Serum galectins and auto-anti-MUC1 antibodies were assessed using ELISA and mucin protein (MUC1) glycan microarrays, and cancer-endothelium adhesion was determined using monolayers of human microvascular lung endothelial cells.Results: The levels of serum galectin-2, -3, -4, and -8 were significantly increased up to 31-fold in patients with cancer and, in particular, those with metastases. As previously shown for galectin-3, the presence of these galectins enhances cancer-endothelium adhesion by interaction with the Thomsen-Friedenreich (TF; Galb1,3GalNAca-) disaccharide on cancer-associated MUC1. This causes MUC1 cell surface polarization, thus exposing underlying adhesion molecules that promote cancer-endothelium adhesion. Elevated circulating galectin-2 levels were associated with increased mortality in patients with colorectal cancer, but this association was suppressed when anti-MUC1 antibodies with specificity for the TF epitope of MUC1 were also present in the circulation.Conclusions: Increased circulation of several members of the galectin family is common in patients with cancer and these may, like circulating galectin-3, also be involved in metastasis promotion. Clin Cancer Res; 17(22); 7035-46. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 82%

Serum Galectin-2, -4, and -8 Are Greatly Increased in Colon and Breast Cancer Patients and Promote Cancer Cell Adhesion to Blood Vascular Endothelium

Barrow

Guo

Wandall

et al. 2011

Clinical Cancer Research

146

136

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“…galectin-7 plays positive and negative roles as a regulator of tumor progression, depending on the histological type of the tumor (18). galectin-8 expression correlates negatively with the development of colon cancer malignancy and this protein is believed to suppress cancer cell migration (19). based on our previous studies (6) and other reports described above, we hypothesized that quantitating the level of circulating galectin proteins could provide valuable insight into the presence of cancers and the state of their progression.…”

Section: Clinical Significance Of Circulating Galectins As Colorectalmentioning

confidence: 85%

Clinical significance of circulating galectins as colorectal cancer markers

et al. 2011

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Abstract. the utility of ceA and cA19-9 as colorectal carcinoma (crc) markers is limited and development of additional reliable markers is under investigation. We previously showed that galectin-1 is overexpressed in crc tissues. If such a protein leaks into the peripheral circulation, it might constitute a tumor marker candidate. Here, we test the hypothesis that the levels of circulating galectins could reflect the presence of crc and/or its progression state. We constructed sandwich elIsAs for galectin-1/-2/-3/-4/-7 and determined their plasma concentrations in 105 crc patients and 100 healthy volunteers (control). Matched pair samples of 56 patients pre-and post-surgery were also subjected to elIsA analysis. circulating levels of galectin-1/-3/-4 in crc patients were significantly higher compared to those in controls. Galectin-1 and galectin-4 levels significantly decreased after surgery (p<0.01), and the level of galectin-4 in most patients fell below the cut-off value. the levels of circulating galectin-4 significantly increased as the tumor stage progressed (P<0.001), whereas those for galectin-1 were relatively high from an early stage. combined use of galectin-4 with ceA and/or cA19-9 markedly increased the proportion of crc patients who were positive for tumor markers (from 33.3 to 59.0% for ceA and from 17.1 to 51.4% for cA19-9). our data show that galectin-4 may be a tumor marker for use in patient follow-up, while galectin-1 could be used for tumor screening. In particular, galectin-4 can be useful as a complementary marker when combined with ceA/cA19-9 to improve crc follow-up.

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“…These different modes of action of galectin-8 are mediated by different signaling pathways, with PI3K and MAPK being the predominant mediators of cell motility induced by immobilized galectin-8, JNK and p21 being key players in mediating the cytostatic effects, and JNK and caspases contributing to the pro-apoptotic effects of this lectin. In view of the cytostatic effects of galectin-8, it is no wonder that a number of tumor cells (66,67), such as malignant colon tissues (68), attenuate the expression of this protein. Still, an interesting question is how galectin-8 is beneficial to invasive prostate carcinomas (58) and other tumors (69) that highly express this lectin.…”

Section: Discussionmentioning

confidence: 99%

Cyclin-dependent Kinase Inhibitors and JNK Act as Molecular Switches, Regulating the Choice between Growth Arrest and Apoptosis Induced by Galectin-8

Arbel-Goren

Levy

Ronen

et al. 2005

Journal of Biological Chemistry

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Galectin-8, a mammalian ␤-galactoside binding lectin, functions as an extracellular matrix protein that forms high affinity interactions with integrins. Here we demonstrated that soluble galectin-8 inhibits cell cycle progression and induces growth arrest. These effects cannot be attributed to interference with cell adhesion but can be attributed to a 4 -5-fold increase in the cellular content of the cyclin-dependent kinase inhibitor p21, which was already evident following a 4-h incubation of H1299 cells with galectin-8. The increase in p21 levels was preceded by a 3-5-fold increase in JNK and protein kinase B (PKB) activities. Accordingly, SP600125, the inhibitor of JNK, and wortmannin, the inhibitor of phosphatidylinositol 3-kinase, which is the upstream activator of PKB, inhibited the increase in the cellular content of p21. Furthermore, overexpression of a dominant inhibitory form of SEK1, the upstream kinase regulator of JNK, inhibited both JNK activation and p21 accumulation. When p21 expression was inhibited by cycloheximide, galectin-8 directed the cells toward apoptosis, which involves induction of poly(ADP-ribose) polymerase cleavage. Indeed, galectin-8-induced apoptosis was 2-fold higher in HTC (p21-null) cells when compared with parental HTC cells. Because overexpression of galectin-8 attenuates the rate of DNA synthesis, stable colonies that overexpress and secrete galectin-8 can be generated only in cells overexpressing a growth factor receptor, such as the insulin receptor. These results implicate galectin-8 as a modulator of cellular growth through up-regulation of p21. This process involves activation of JNK, which enhances the synthesis of p21, combined with the activation of PKB, which inhibits p21 degradation. These effects of the lectin depended upon protein-sugar interactions and were induced when galectin-8 was present as a soluble ligand or when it was overexpressed in cells.

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Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor

Cited by 113 publications

References 44 publications

Serum Galectin-2, -4, and -8 Are Greatly Increased in Colon and Breast Cancer Patients and Promote Cancer Cell Adhesion to Blood Vascular Endothelium

Serum Galectin-2, -4, and -8 Are Greatly Increased in Colon and Breast Cancer Patients and Promote Cancer Cell Adhesion to Blood Vascular Endothelium

Clinical significance of circulating galectins as colorectal cancer markers

Cyclin-dependent Kinase Inhibitors and JNK Act as Molecular Switches, Regulating the Choice between Growth Arrest and Apoptosis Induced by Galectin-8

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