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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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Expression of ppGalNAc-T2 mRNA in human tumor cells. (A) The mRNA level of ppGalNAc-T2was detected by RT-PCR. (B) The intensity of PCR product was normalized againstβ-actin. 1, SHG44 cells; 2, SGC7901 cells; 3, SHI-1 cells; 4, A549 cells; and 5,HO8910 cells.
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f1-ijmm-30-06-1267: Expression of ppGalNAc-T2 mRNA in human tumor cells. (A) The mRNA level of ppGalNAc-T2was detected by RT-PCR. (B) The intensity of PCR product was normalized againstβ-actin. 1, SHG44 cells; 2, SGC7901 cells; 3, SHI-1 cells; 4, A549 cells; and 5,HO8910 cells.

Mentions: To investigate the potential role of ppGalNAc-T2 in human malignant tumors, we firstdetected the expression panel of ppGalNAc-T2 in 5 types of poorly differentiated malignanttumor cell lines. The mRNA level of ppGalNAc-T2 in these cells was determined by RT-PCR.All poorly differentiated tumor cells which have aberrant terminal sugar structures ofO-glycan chains, including SGC7901 gastric cancer, SHG44 glioma, SHI-1 leukemia, A549 lungadenocarcinoma, and HO8910 ovarian cancer cells expressed ppGalNAc-T2 (Fig. 1). Thus ppGalNAc-T2 may be markersfor poorly differentiated carcinomas. In addition, we found that ppGalNAc-T2 mRNA wasdifferentially expressed, as shown in Fig.1A. The mRNA expression ratios (ppGalNAc-T2/β-actin) were0.38±0.016, 1.23±0.017, 0.82±0.035, 0.69±0.014 and0.78±0.023, respectively. The results showed that ppGalNAc-T2 expression inSGC7901 cells was higher than in other cells (P<0.05) (Fig. 1B), suggesting that this gene mayplay a key role in gastric tumorigenesis. We therefore used gastric cancer as our researchmodel to determine whether ppGalNAc-T2 is correlated with cell invasion andmetastasis.


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)

Expression of ppGalNAc-T2 mRNA in human tumor cells. (A) The mRNA level of ppGalNAc-T2was detected by RT-PCR. (B) The intensity of PCR product was normalized againstβ-actin. 1, SHG44 cells; 2, SGC7901 cells; 3, SHI-1 cells; 4, A549 cells; and 5,HO8910 cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-ijmm-30-06-1267: Expression of ppGalNAc-T2 mRNA in human tumor cells. (A) The mRNA level of ppGalNAc-T2was detected by RT-PCR. (B) The intensity of PCR product was normalized againstβ-actin. 1, SHG44 cells; 2, SGC7901 cells; 3, SHI-1 cells; 4, A549 cells; and 5,HO8910 cells.
Mentions: To investigate the potential role of ppGalNAc-T2 in human malignant tumors, we firstdetected the expression panel of ppGalNAc-T2 in 5 types of poorly differentiated malignanttumor cell lines. The mRNA level of ppGalNAc-T2 in these cells was determined by RT-PCR.All poorly differentiated tumor cells which have aberrant terminal sugar structures ofO-glycan chains, including SGC7901 gastric cancer, SHG44 glioma, SHI-1 leukemia, A549 lungadenocarcinoma, and HO8910 ovarian cancer cells expressed ppGalNAc-T2 (Fig. 1). Thus ppGalNAc-T2 may be markersfor poorly differentiated carcinomas. In addition, we found that ppGalNAc-T2 mRNA wasdifferentially expressed, as shown in Fig.1A. The mRNA expression ratios (ppGalNAc-T2/β-actin) were0.38±0.016, 1.23±0.017, 0.82±0.035, 0.69±0.014 and0.78±0.023, respectively. The results showed that ppGalNAc-T2 expression inSGC7901 cells was higher than in other cells (P<0.05) (Fig. 1B), suggesting that this gene mayplay a key role in gastric tumorigenesis. We therefore used gastric cancer as our researchmodel to determine whether ppGalNAc-T2 is correlated with cell invasion andmetastasis.

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