Galectin-3 regulates p21 stability in human prostate cancer cells

Wang, Yi; Balan, Vitaly; Kho, Dhonghyo; Hogan, Victor; Nangia‐Makker, Pratima; Raz, Avraham

doi:10.1038/onc.2012.528

Cited by 21 publications

(15 citation statements)

References 49 publications

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“…The adhesion of platelets to HT29 cells was associated with a transient upregulation of p21 WAF1/CIP1 protein, possibly through the activation of transcriptional or posttranscriptional regulatory mechanisms (Wang et al, 2012), which necessitate further investigation. This effect was unlikely due to released TGF-b1 because 1) the cytokine was released later than p21 WAF1/CIP1 protein induction, and 2) HT29 cells have been previously shown to be insensitive to p21 WAF1/CIP1 induction after TGF-b treatment (Li et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of Platelet-Tumor Cell Cross-Talk Prevents Platelet-Induced Overexpression of Cyclooxygenase-2 in HT29 Human Colon Carcinoma Cells

et al. 2013

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Cyclooxygenase (COX)-2-derived prostanoids can influence several processes that are linked to carcinogenesis. We aimed to address the hypothesis that platelets contribute to aberrant COX-2 expression in HT29 colon carcinoma cells and to reveal the role of platelet-induced COX-2 on the expression of proteins involved in malignancy and marker genes of epithelialmesenchymal transition (EMT). Human platelets cocultured with HT29 cells rapidly adhered to cancer cells and induced COX-2 mRNA expression, but not protein synthesis, which required the late release of platelet-derived growth factor and COX-2 mRNA stabilization. Platelet-induced COX-2-dependent prostaglandin E 2 (PGE 2 ) synthesis in HT29 cells was involved in the downregulation of p21 WAF1/CIP1 and the upregulation of cyclinB1 since these effects were prevented by rofecoxib (a selective COX-2 inhibitor) and rescued by exogenous PGE 2 . Galectin-3, which is highly expressed in HT29 cells, is unique among galectins because it contains a collagen-like domain. Thus, we studied the role of galectin-3 and platelet collagen receptors in plateletinduced COX-2 overexpression. Inhibitors of galectin-3 function (b-lactose, a dominant-negative form of galectin-3, Gal-3C, and anti-galectin-3 antibody M3/38) or collagen receptor-mediated platelet adhesion (revacept, a dimeric platelet collagen receptor GPVI-Fc) prevented aberrant COX-2 expression. Inhibition of platelet-cancer cell interaction by revacept was more effective than rofecoxib in preventing platelet-induced mRNA changes of EMT markers, suggesting that direct cell-cell contact and aberrant COX-2 expression synergistically induced gene expression modifications associated with EMT. In conclusion, our findings provide the rationale for testing blockers of collagen binding sites, such as revacept, and galectin-3 inhibitors in the prevention of colon cancer metastasis in animal models, followed by studies in patients.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of Platelet-Tumor Cell Cross-Talk Prevents Platelet-Induced Overexpression of Cyclooxygenase-2 in HT29 Human Colon Carcinoma Cells

et al. 2013

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“…Recently, several markers like galectin 3, circulating microRNAs, and integrins were discussed as new prognostic biomarkers [4][5][6][7]. Integrins are transmembrane receptors that mediate cell signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Correlation between the expression of integrins in prostate cancer and clinical outcome in 1284 patients

Heß¹,

Böger²,

Behrens³

et al. 2014

Annals of Diagnostic Pathology

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The aim of this study was to investigate the expression of a panel of integrins in prostate cancer in order to explore their potential for tumor biology. Formalin-fixed and paraffin-embedded tissue samples of 1284 prostate cancer patients were retrieved from the archive of the Department of Pathology. Immunostaining was done with rabbit monoclonal antibodies directed against αvβ3, αvβ5, αvβ6, αvβ8, β3, and αv-pan. Staining results were correlated with clinicopathologic patient characteristics and patient survival. Immunostaining of tumor cells performed on whole tissue sections of 52 patients was sparse for αvβ3, αvβ6, and αvβ8, and more prevalent for αvβ5 and αv-pan. αvβ5, αvβ8, and αv-pan were selected for further analyses in tissue microarrays representing the entire study cohort. αvβ8 staining was generally observed in peripheral nerves. αvβ5 and αv-pan provided strong evidence for the differential expression of these integrins in prostate cancer. The expression was variable with regard to the histoanatomical/cytoanatomical localization, cell type, intensity of immunolabeling, and Gleason pattern. αvβ5 and αv-pan are differentially expressed in prostate cancer, and the differentiation of prostate cancer seems to influence integrin expression and subcellular distribution.

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“…24 In bacterial interactions, galectin‐3 can bind directly to pathogens by serving as a crosslinker for microorganisms or as a cellular docking site;25, 26 it can also act as a scaffold for the presentation of ligands such as lipopolysaccharides into an aggregate that stimulates cellular responses 24. In cancer, although the effects of multivalency in some systems are not known, galectin‐3 has been shown to regulate the expression of proteins such as p21 (a regulator of the cell cycle) by stabilizing the p21 protein 27. In galectin binding studies with neuroblastoma cells, high affinity and selective binding of galectins was only observed when both the glycan ligand and the display of the ligand on the cell surface were optimized, thus strongly indicating that multivalent display of galectin‐3 is of critical importance 28.…”

Section: Introductionmentioning

confidence: 99%

Lactose‐Functionalized Dendrimers Arbitrate the Interaction of Galectin‐3/MUC1 Mediated Cancer Cellular Aggregation

et al. 2014

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By using lactose-functionalized poly(amidoamine) dendrimers as a tunable multivalent platform, we studied cancer cell aggregation in three different cell lines (A549, DU-145, and HT-1080) with galectin-3. We found that small lactose-functionalized G(2)-dendrimer 1 inhibited galectin-3-induced aggregation of the cancer cells. In contrast, dendrimer 4 (a larger, generation 6 dendrimer with 100 carbohydrate end groups) caused cancer cells to aggregate through a galectin-3 pathway. This study indicates that inhibition of cellular aggregation occurred because 1 provided competitive binding sites for galectin-3 (compared to its putative cancer cell ligand, TF-antigen on MUC1). Dendrimer 4, in contrast, provided an excess of ligands for galectin-3 binding; this caused crosslinking and aggregation of cells to be increased.

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Galectin-3 regulates p21 stability in human prostate cancer cells

Cited by 21 publications

References 49 publications

Pharmacological Inhibition of Platelet-Tumor Cell Cross-Talk Prevents Platelet-Induced Overexpression of Cyclooxygenase-2 in HT29 Human Colon Carcinoma Cells

Pharmacological Inhibition of Platelet-Tumor Cell Cross-Talk Prevents Platelet-Induced Overexpression of Cyclooxygenase-2 in HT29 Human Colon Carcinoma Cells

Correlation between the expression of integrins in prostate cancer and clinical outcome in 1284 patients

Lactose‐Functionalized Dendrimers Arbitrate the Interaction of Galectin‐3/MUC1 Mediated Cancer Cellular Aggregation

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