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Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis-associated behavior in gastric cancer.

Hua D, Shen L, Xu L, Jiang Z, Zhou Y, Yue A, Zou S, Cheng Z, Wu S - Int. J. Mol. Med. (2012)

Bottom Line: We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells.However, it did not exhibit any apparent correlation with MMP-14 expression levels.Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1.

View Article: PubMed Central - PubMed

Affiliation: Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.

ABSTRACT
Aberrant glycosylation of cell surface glycoprotein due to specific alterations of glycosyltransferase activity is usually associated with invasion and metastasis of cancer, particularly of gastric carcinomas. Polypeptide N-acetylgalactosaminyltransferase 2 (ppGalNAc-T2), which catalyzes initiation of mucin-type O-glycosylation, is also involved in tumor migration and invasion. However, a comprehensive understanding of how ppGalNAc-T2 correlates with the metastasic potential of human gastric cancer is not currently available. In the present study, ppGalNAc-T2 was detected in a variety of human poorly differentiated tumor cells, and expression appeared to be higher in SGC7901 gastric cancer cells. In addition, we investigated the potential effects of ppGalNAc-T2 on growth and metastasis-associated behavior in SGC7901 cells after stable transfection with ppGalNAc-T2 sense and antisense vectors. We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells. Therefore, we attempted to clarify the mechanisms underlying the anti-metastatic activities of ppGalNAc-T2. Further investigation indicated that overexpression of ppGalNAc-T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2 expression at both the protein and mRNA levels, which may be associated with ppGalNAc-T2 suppressing the expression of transforming growth factor (TGF)-β1. However, it did not exhibit any apparent correlation with MMP-14 expression levels. Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1. These results indicate that ppGalNAc‑T2 may be used as a novel therapeutic target for human gastric cancer treatment.

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Comparison of in vitro invasiveness of cells. The invitro invasion of SGC7901 cells and their transfectants was measured bydetermined cell counts that penetrated through Matrigel-coated Transwell chambers (12-Ampore size). The experiments are representative of 3 independent experiments with similarresults. 1, untreated SGC7901 cells; 2, SGC7901-T2s group; 3, control group; and 4,SGC7901-T2as group. (*P<0.05,#P>0.05 compared to the untreated group).
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f6-ijmm-30-06-1267: Comparison of in vitro invasiveness of cells. The invitro invasion of SGC7901 cells and their transfectants was measured bydetermined cell counts that penetrated through Matrigel-coated Transwell chambers (12-Ampore size). The experiments are representative of 3 independent experiments with similarresults. 1, untreated SGC7901 cells; 2, SGC7901-T2s group; 3, control group; and 4,SGC7901-T2as group. (*P<0.05,#P>0.05 compared to the untreated group).

Mentions: Since ECM degradation is key to tumor cell invasion, the in vitroinvasiveness of these cell lines through Matrigel coated membranes was compared. Differentinvasiveness was observed in the control, untreated, as well as the SGC7901-T2s andSGC7901-T2as group cells, respectively (Fig.6). The control group cells showed little invasion in comparison to the untreatedcells (P>0.05), whereas overexpression of ppGalNAc-T2 in SGC7901-T2s cellsdecreased their migratory capacity (P<0.05). By contrast, downregulation ofppGalNAc-T2 increased the invasive ability in the SGC7901-T2as group (P<0.05).These results suggested that ppGalNAc-T2 expression was inversely associated with theinvasiveness of cells in vitro. The inverse correlation tendency betweenppGalNAc-T2 expression in SGC7901 cells and their in vitro invasiveability indicates that ppGalNAc-T2 is likely to be a metastasis suppressor gene inSGC7901.


Polypeptide N-acetylgalactosaminyltransferase 2 regulates cellular metastasis-associated behavior in gastric cancer.

Hua D, Shen L, Xu L, Jiang Z, Zhou Y, Yue A, Zou S, Cheng Z, Wu S - Int. J. Mol. Med. (2012)

Comparison of in vitro invasiveness of cells. The invitro invasion of SGC7901 cells and their transfectants was measured bydetermined cell counts that penetrated through Matrigel-coated Transwell chambers (12-Ampore size). The experiments are representative of 3 independent experiments with similarresults. 1, untreated SGC7901 cells; 2, SGC7901-T2s group; 3, control group; and 4,SGC7901-T2as group. (*P<0.05,#P>0.05 compared to the untreated group).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042861&req=5

f6-ijmm-30-06-1267: Comparison of in vitro invasiveness of cells. The invitro invasion of SGC7901 cells and their transfectants was measured bydetermined cell counts that penetrated through Matrigel-coated Transwell chambers (12-Ampore size). The experiments are representative of 3 independent experiments with similarresults. 1, untreated SGC7901 cells; 2, SGC7901-T2s group; 3, control group; and 4,SGC7901-T2as group. (*P<0.05,#P>0.05 compared to the untreated group).
Mentions: Since ECM degradation is key to tumor cell invasion, the in vitroinvasiveness of these cell lines through Matrigel coated membranes was compared. Differentinvasiveness was observed in the control, untreated, as well as the SGC7901-T2s andSGC7901-T2as group cells, respectively (Fig.6). The control group cells showed little invasion in comparison to the untreatedcells (P>0.05), whereas overexpression of ppGalNAc-T2 in SGC7901-T2s cellsdecreased their migratory capacity (P<0.05). By contrast, downregulation ofppGalNAc-T2 increased the invasive ability in the SGC7901-T2as group (P<0.05).These results suggested that ppGalNAc-T2 expression was inversely associated with theinvasiveness of cells in vitro. The inverse correlation tendency betweenppGalNAc-T2 expression in SGC7901 cells and their in vitro invasiveability indicates that ppGalNAc-T2 is likely to be a metastasis suppressor gene inSGC7901.

Bottom Line: We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells.However, it did not exhibit any apparent correlation with MMP-14 expression levels.Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1.

View Article: PubMed Central - PubMed

Affiliation: Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.

ABSTRACT
Aberrant glycosylation of cell surface glycoprotein due to specific alterations of glycosyltransferase activity is usually associated with invasion and metastasis of cancer, particularly of gastric carcinomas. Polypeptide N-acetylgalactosaminyltransferase 2 (ppGalNAc-T2), which catalyzes initiation of mucin-type O-glycosylation, is also involved in tumor migration and invasion. However, a comprehensive understanding of how ppGalNAc-T2 correlates with the metastasic potential of human gastric cancer is not currently available. In the present study, ppGalNAc-T2 was detected in a variety of human poorly differentiated tumor cells, and expression appeared to be higher in SGC7901 gastric cancer cells. In addition, we investigated the potential effects of ppGalNAc-T2 on growth and metastasis-associated behavior in SGC7901 cells after stable transfection with ppGalNAc-T2 sense and antisense vectors. We found that cell proliferation, adhesion and invasion were decreased in ppGalNAc-T2 overexpressed cells but increased in ppGalNAc-T2 downregulated cells. Therefore, we attempted to clarify the mechanisms underlying the anti-metastatic activities of ppGalNAc-T2. Further investigation indicated that overexpression of ppGalNAc-T2 is involved in the inhibition of matrix metalloproteinase (MMP)-2 expression at both the protein and mRNA levels, which may be associated with ppGalNAc-T2 suppressing the expression of transforming growth factor (TGF)-β1. However, it did not exhibit any apparent correlation with MMP-14 expression levels. Our data show the effect of ppGalNAc-T2 on proliferation, adhesion or invasion of SGC7901 gastric cancer cells, suggesting that ppGalNAc-T2 may exert anti-proliferative and anti-metastatic activity through the decrease of MMP-2 and TGF-β1. These results indicate that ppGalNAc‑T2 may be used as a novel therapeutic target for human gastric cancer treatment.

Show MeSH
Related in: MedlinePlus