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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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In vitro adhesion of SGC7901 cells in the presence of (A) Matrigel,(B) HA and (C) FN at different time points. The cells (5x103) were added to a96-well plate coated with HA, FN or Matrigel, and the cells were incubated at 0.5, 1 and1.5 h intervals. The number of attached cells was calculated by the MTT assay. Resultsshowed that overexpression of ppGalNAc-T2 inhibits cell adhesion. Values are expressedas the mean ± SD of three independent experiments.(*P<0.05, **P>0.05compared to the untreated cells at 0.5 h; #P<0.05,##P>0.05 compared to the untreated cells at 1 h;▵P<0.05, ▵▵P>0.05compared to the untreated cells at 1.5 h).
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f5-ijmm-30-06-1267: In vitro adhesion of SGC7901 cells in the presence of (A) Matrigel,(B) HA and (C) FN at different time points. The cells (5x103) were added to a96-well plate coated with HA, FN or Matrigel, and the cells were incubated at 0.5, 1 and1.5 h intervals. The number of attached cells was calculated by the MTT assay. Resultsshowed that overexpression of ppGalNAc-T2 inhibits cell adhesion. Values are expressedas the mean ± SD of three independent experiments.(*P<0.05, **P>0.05compared to the untreated cells at 0.5 h; #P<0.05,##P>0.05 compared to the untreated cells at 1 h;▵P<0.05, ▵▵P>0.05compared to the untreated cells at 1.5 h).

Mentions: Adhesion is a key event in the metastasic process where cells must first adhere to theECM prior to its degradation. To examine whether ppGalNAc-T2 expression is associated withadhesion of gastric cancer, in vitro adhesion assay was carried out toevaluate the adhesive ability of the untreated SGC7901, control, SGC7901-T2s andSGC7901-T2as cells. The ability of cell adhesion in the SGC7901-T2s group cells wasdecreased compared with untreated or control SGC7901 cells (P<0.05), but increasedin the SGC7901-T2as group cells at different time points (P<0.05) (Figs. 5A, 5B and 5C).


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)

In vitro adhesion of SGC7901 cells in the presence of (A) Matrigel,(B) HA and (C) FN at different time points. The cells (5x103) were added to a96-well plate coated with HA, FN or Matrigel, and the cells were incubated at 0.5, 1 and1.5 h intervals. The number of attached cells was calculated by the MTT assay. Resultsshowed that overexpression of ppGalNAc-T2 inhibits cell adhesion. Values are expressedas the mean ± SD of three independent experiments.(*P<0.05, **P>0.05compared to the untreated cells at 0.5 h; #P<0.05,##P>0.05 compared to the untreated cells at 1 h;▵P<0.05, ▵▵P>0.05compared to the untreated cells at 1.5 h).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5-ijmm-30-06-1267: In vitro adhesion of SGC7901 cells in the presence of (A) Matrigel,(B) HA and (C) FN at different time points. The cells (5x103) were added to a96-well plate coated with HA, FN or Matrigel, and the cells were incubated at 0.5, 1 and1.5 h intervals. The number of attached cells was calculated by the MTT assay. Resultsshowed that overexpression of ppGalNAc-T2 inhibits cell adhesion. Values are expressedas the mean ± SD of three independent experiments.(*P<0.05, **P>0.05compared to the untreated cells at 0.5 h; #P<0.05,##P>0.05 compared to the untreated cells at 1 h;▵P<0.05, ▵▵P>0.05compared to the untreated cells at 1.5 h).
Mentions: Adhesion is a key event in the metastasic process where cells must first adhere to theECM prior to its degradation. To examine whether ppGalNAc-T2 expression is associated withadhesion of gastric cancer, in vitro adhesion assay was carried out toevaluate the adhesive ability of the untreated SGC7901, control, SGC7901-T2s andSGC7901-T2as cells. The ability of cell adhesion in the SGC7901-T2s group cells wasdecreased compared with untreated or control SGC7901 cells (P<0.05), but increasedin the SGC7901-T2as group cells at different time points (P<0.05) (Figs. 5A, 5B and 5C).

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