High expression of α 2, 3-linked sialic acid residues is associated with the metastatic potential of human gastric cancer

Wang, Fengling; Cui, Shu‐Xiang; Sun, Lan-Ping; Qu, Xian‐Jun; Xie, Ying; Zhou, Lixin; Mu, Yuguang; Tang, Wei; Wang, Yuanshu

doi:10.1016/j.cdp.2009.01.001

Cited by 59 publications

(48 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Second these molecules are not specifically present on the surface of cancer cells, but are also present on non-cancer cells. Sialic acid, often increased on the surface of cancer cells, might even protect cancer cells and metastases [56][57][58] against anticancer drugs, besides being a target for the peptides. It was reported that neuraminidasetreated U937 cells were less susceptible to permeabilization by BMAP peptides, suggesting that the sialyl moieties might be initial interaction sites of these peptides with the cells [33].…”

Section: Discussionmentioning

confidence: 99%

Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine

Riedl

Leber

Rinner

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

Host defense-derived peptides have emerged as a novel strategy for the development of alternative anticancer therapies. In this study we report on characteristic features of human lactoferricin (hLFcin) derivatives which facilitate specific killing of cancer cells of melanoma, glioblastoma and rhabdomyosarcoma compared with non-specific derivatives and the synthetic peptide RW-AH. Changes in amino acid sequence of hLFcin providing 9-11 amino acids stretched derivatives LF11-316, -318 and -322 only yielded low antitumor activity. However, the addition of the repeat (di-peptide) and the retro-repeat (di-retro-peptide) sequences highly improved cancer cell toxicity up to 100% at 20 μM peptide concentration. Compared to the complete parent sequence hLFcin the derivatives showed toxicity on the melanoma cell line A375 increased by 10-fold and on the glioblastoma cell line U-87mg by 2-3-fold. Reduced killing velocity, apoptotic blebbing, activation of caspase 3/7 and formation of apoptotic DNA fragments proved that the active and cancer selective peptides, e.g. R-DIM-P-LF11-322, trigger apoptosis, whereas highly active, though non-selective peptides, such as DIM-LF11-318 and RW-AH seem to kill rapidly via necrosis inducing membrane lyses. Structural studies revealed specific toxicity on cancer cells by peptide derivatives with loop structures, whereas non-specific peptides comprised α-helical structures without loop. Model studies with the cancer membrane mimic phosphatidylserine (PS) gave strong evidence that PS only exposed by cancer cells is an important target for specific hLFcin derivatives. Other negatively charged membrane exposed molecules as sialic acid, heparan and chondroitin sulfate were shown to have minor impact on peptide activity.

show abstract

Section: Discussionmentioning

confidence: 99%

Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine

Riedl

Leber

Rinner

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

View full text Add to dashboard Cite

show abstract

“…In our previous study, we examined the levels of sialylation of the glycoconjugate in gastric cancer using Maackia amurensis leukoagglutinin (MAL), a lectin that specifically recognizes the trisaccharide sequence NeuAca2,3Gal b1,4GlcNAc/Glc [4]. The connection between MAL staining and the behavior of invasion and metastasis of cancer cells was analyzed [5,6]. The results showed that the number of MAL-positive cells is significantly increased in gastric cancers, and the extent of MAL staining is associated with the progress of invasion and metastasis of gastric cancers [5].…”

Section: Introductionmentioning

confidence: 99%

Altered mRNA expressions of sialyltransferases in human gastric cancer tissues

Wang

Xie

et al. 2010

Med Oncol

View full text Add to dashboard Cite

Aberrant sialylation and altered sialyltransferase (ST) expressions are frequently found in many types of cancer. In this study, we examined the expressions of α 2,3-linked sialic acid residues and STs mRNA in human gastric cancer tissues. The relationship between the levels of α 2,3-linked sialic acid residues and the expression of STs mRNA was also analyzed. Maackia amurensis leukoagglutinin (MAL) specific for α 2,3-linked sialic acid was used for immunohistochemical staining. All gastric cancer tissues were positive for MAL staining, whereas adjacent normal tissues were negative. The extent of MAL staining was significantly correlated with the behavior of gastric cancer. The expression of STs mRNA was examined by real-time quantitative reverse transcription-polymerase chain reaction assay. The levels of ST3Gal IV and ST6GalI in gastric cancer tissues were significantly increased compared with those in adjacent normal tissues (P < 0.05), whereas the levels of ST3Gal I, ST3Gal III, and ST3Gal VI were not increased. Furthermore, the high expression of ST3Gal IV was closely related to the extent of MAL staining (P < 0.05) unlike that of ST6Gal I. These results indicated that gastric cancer tissues expressed high levels of α 2,3-linked sialic acid residues, ST3Gal IV, and ST6Gal I. The high expression of ST3Gal IV may contribute to the expression of α 2,3-linked sialic acid residues, which is associated with the malignant behavior of gastric cancer cells.

show abstract

“…Metastasis is a selective process by which certain tumor cells disseminate to form secondary foci at distant sites (1,2). Tumor cell metastasis requires alterations in membrane properties determined by cell surface glycoconjugates (3,4). The biosynthesis of carbohydrate structures is tissue-specific and developmentally regulated by glycosyltransferases (5).…”

Section: Introductionmentioning

confidence: 99%

Glycan-related gene expression signatures in human metastatic hepatocellular carcinoma cells

Kang

Wang

Chen

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Human hepatocellular carcinoma (HCC) ranks second in cancer mortality in China; recurrence and metastasis have been the cause of the high mortality. Glycans on the cell surface play a pivotal role in tumor metastasis. The global alteration in the structure and composition of N-glycans during HCC metastasis remains unknown. To understand glycan alterations of glycoproteins by correlating the glycosyltransferase expression profile with glycan structure, we systematically used glycan profiling tools: glycogene microarray analyses of 115 genes, including glycotransferases, glycosidases and nuclear sugar transporters and lectin chips to investigate the glycan-related gene expression signatures in the high metastatic potential HCC cell line, HCCLM3, in comparison to the HCC cell line, Hep3B, with low metastatic potential. Of the 115 genes, 18 genes were up-regulated in high metastatic potential HCCLM3 cells in comparison to Hep3B cells, while 11 genes were down-regulated. The differentially expressed genes, such as ST3GalI, FUT8, β3GalT5, MGAT3 and MGAT5, were mainly involved in the synthesis of N-glycan and glycolipids, particularly the sialyl Lewis antigen. The results of the glycogene microarray analysis were further validated by quantitative real-time PCR analysis and lectin-based analysis. The differentially expressed glycogenes identified in this study may provide new insights and represent novel factors for investigating the functional role of cell surface carbohydrate-mediated HCC metastasis.

show abstract

High expression of α 2, 3-linked sialic acid residues is associated with the metastatic potential of human gastric cancer

Cited by 59 publications

References 36 publications

Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine

Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine

Altered mRNA expressions of sialyltransferases in human gastric cancer tissues

Glycan-related gene expression signatures in human metastatic hepatocellular carcinoma cells

Contact Info

Product

Resources

About