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Enhancement of metastatic ability by ectopic expression of ST6GalNAcI on a gastric cancer cell line in a mouse model.

Ozaki H, Matsuzaki H, Ando H, Kaji H, Nakanishi H, Ikehara Y, Narimatsu H - Clin. Exp. Metastasis (2012)

Bottom Line: Then, sTn-carrying proteins were immunoprecipitated from culture supernatants and lysates of these cells, and identified MUC1 and CD44 as major sTn carriers.It was confirmed that MUC1 carries sTn also in human advanced gastric cancer tissues.Identification of sTn carrier proteins will help understand mechanisms of metastatic phenotype acquisition of gastric cancer cells by ST6GalNAcI and sTn.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.

ABSTRACT
ST6GalNAcI is a sialyltransferase responsible for the synthesis of sialyl Tn (sTn) antigen which is expressed in a variety of adenocarcinomas including gastric cancer especially in advanced cases, but the roles of ST6GalNAcI and sTn in cancer progression are largely unknown. We generated sTn-expressing human gastric cancer cells by ectopic expression of ST6GalNAcI to evaluate metastatic ability of these cells and prognostic effect of ST6GalNAcI and sTn in a mouse model, and identified sTn carrier proteins to gain insight into the function of ST6GalNAcI and sTn in gastric cancer progression. A green fluorescent protein-tagged human gastric cancer cell line was transfected with ST6GalNAcI to produce sTn-expressing cells, which were transplanted into nude mice. STn-positive gastric cancer cells showed higher intraperitoneal metastatic ability in comparison with sTn-negative control, resulting in shortened survival time of the mice, which was mitigated by anti-sTn antibody administration. Then, sTn-carrying proteins were immunoprecipitated from culture supernatants and lysates of these cells, and identified MUC1 and CD44 as major sTn carriers. It was confirmed that MUC1 carries sTn also in human advanced gastric cancer tissues. Identification of sTn carrier proteins will help understand mechanisms of metastatic phenotype acquisition of gastric cancer cells by ST6GalNAcI and sTn.

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Effects of B72.3 administration on metastatic ability and survival of the recipient mice. a GFP-fluorescence view of peritoneal metastasis. Intraperitoneal dissemination such as peri-bile duct invasion (arrow), a cause of jaundice was reduced by B72.3 treatment. b Metastatic tumor weights excised from control mouse IgG-treated and B72.3-treated mice. c The incidence of jaundice was significantly lower in B72.3-treated mice than in IgG-treated control. *P < 0.05. d Overall survival of the GCIY/6L-transplanted recipient mice as depicted by the Kaplan-Meier method. The recipients administered with B72.3 (open circles) survived significantly longer than those with control mouse IgG (closed circles). P < 0.05; n = 6
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Fig3: Effects of B72.3 administration on metastatic ability and survival of the recipient mice. a GFP-fluorescence view of peritoneal metastasis. Intraperitoneal dissemination such as peri-bile duct invasion (arrow), a cause of jaundice was reduced by B72.3 treatment. b Metastatic tumor weights excised from control mouse IgG-treated and B72.3-treated mice. c The incidence of jaundice was significantly lower in B72.3-treated mice than in IgG-treated control. *P < 0.05. d Overall survival of the GCIY/6L-transplanted recipient mice as depicted by the Kaplan-Meier method. The recipients administered with B72.3 (open circles) survived significantly longer than those with control mouse IgG (closed circles). P < 0.05; n = 6

Mentions: To confirm the involvement of sTn in the peritoneal metastasis in this model, we tried to suppress the peritoneal metastasis of GCIY/6L and to prolong survival time of the mice by administration of anti-sTn mAb, B72.3. One milligram of purified B72.3, or purified mouse IgG was injected into the peritoneal cavity of the recipient mice twice a week for 3 weeks after injection of GCIY/6L cells (4 × 106 per mouse). As shown in Fig. 3a, the number and the sizes of peritoneal metastatic foci tended to be smaller in B72.3-treated mice than in control mice. In accordance with this observation, incidence of jaundice due to the obstruction of biliary tract, which is associated with the progression of tumor invasion, was significantly lower in B72.3-treated mice than controls, while incidence of ascites accumulation was not different between the two groups (Fig. 3c). However, we did not detect significant difference in metastatic tumor weights between B72.3-treated and control groups in this experimental condition (Fig. 3b). Nevertheless, survival time of the mice was significantly longer for B72.3-treated mice than controls (Fig. 3d). These results suggest possible involvement of sTn in the augmented metastatic property of gastric cancer cells in this mouse model.Fig. 3


Enhancement of metastatic ability by ectopic expression of ST6GalNAcI on a gastric cancer cell line in a mouse model.

Ozaki H, Matsuzaki H, Ando H, Kaji H, Nakanishi H, Ikehara Y, Narimatsu H - Clin. Exp. Metastasis (2012)

Effects of B72.3 administration on metastatic ability and survival of the recipient mice. a GFP-fluorescence view of peritoneal metastasis. Intraperitoneal dissemination such as peri-bile duct invasion (arrow), a cause of jaundice was reduced by B72.3 treatment. b Metastatic tumor weights excised from control mouse IgG-treated and B72.3-treated mice. c The incidence of jaundice was significantly lower in B72.3-treated mice than in IgG-treated control. *P < 0.05. d Overall survival of the GCIY/6L-transplanted recipient mice as depicted by the Kaplan-Meier method. The recipients administered with B72.3 (open circles) survived significantly longer than those with control mouse IgG (closed circles). P < 0.05; n = 6
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3275730&req=5

Fig3: Effects of B72.3 administration on metastatic ability and survival of the recipient mice. a GFP-fluorescence view of peritoneal metastasis. Intraperitoneal dissemination such as peri-bile duct invasion (arrow), a cause of jaundice was reduced by B72.3 treatment. b Metastatic tumor weights excised from control mouse IgG-treated and B72.3-treated mice. c The incidence of jaundice was significantly lower in B72.3-treated mice than in IgG-treated control. *P < 0.05. d Overall survival of the GCIY/6L-transplanted recipient mice as depicted by the Kaplan-Meier method. The recipients administered with B72.3 (open circles) survived significantly longer than those with control mouse IgG (closed circles). P < 0.05; n = 6
Mentions: To confirm the involvement of sTn in the peritoneal metastasis in this model, we tried to suppress the peritoneal metastasis of GCIY/6L and to prolong survival time of the mice by administration of anti-sTn mAb, B72.3. One milligram of purified B72.3, or purified mouse IgG was injected into the peritoneal cavity of the recipient mice twice a week for 3 weeks after injection of GCIY/6L cells (4 × 106 per mouse). As shown in Fig. 3a, the number and the sizes of peritoneal metastatic foci tended to be smaller in B72.3-treated mice than in control mice. In accordance with this observation, incidence of jaundice due to the obstruction of biliary tract, which is associated with the progression of tumor invasion, was significantly lower in B72.3-treated mice than controls, while incidence of ascites accumulation was not different between the two groups (Fig. 3c). However, we did not detect significant difference in metastatic tumor weights between B72.3-treated and control groups in this experimental condition (Fig. 3b). Nevertheless, survival time of the mice was significantly longer for B72.3-treated mice than controls (Fig. 3d). These results suggest possible involvement of sTn in the augmented metastatic property of gastric cancer cells in this mouse model.Fig. 3

Bottom Line: Then, sTn-carrying proteins were immunoprecipitated from culture supernatants and lysates of these cells, and identified MUC1 and CD44 as major sTn carriers.It was confirmed that MUC1 carries sTn also in human advanced gastric cancer tissues.Identification of sTn carrier proteins will help understand mechanisms of metastatic phenotype acquisition of gastric cancer cells by ST6GalNAcI and sTn.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.

ABSTRACT
ST6GalNAcI is a sialyltransferase responsible for the synthesis of sialyl Tn (sTn) antigen which is expressed in a variety of adenocarcinomas including gastric cancer especially in advanced cases, but the roles of ST6GalNAcI and sTn in cancer progression are largely unknown. We generated sTn-expressing human gastric cancer cells by ectopic expression of ST6GalNAcI to evaluate metastatic ability of these cells and prognostic effect of ST6GalNAcI and sTn in a mouse model, and identified sTn carrier proteins to gain insight into the function of ST6GalNAcI and sTn in gastric cancer progression. A green fluorescent protein-tagged human gastric cancer cell line was transfected with ST6GalNAcI to produce sTn-expressing cells, which were transplanted into nude mice. STn-positive gastric cancer cells showed higher intraperitoneal metastatic ability in comparison with sTn-negative control, resulting in shortened survival time of the mice, which was mitigated by anti-sTn antibody administration. Then, sTn-carrying proteins were immunoprecipitated from culture supernatants and lysates of these cells, and identified MUC1 and CD44 as major sTn carriers. It was confirmed that MUC1 carries sTn also in human advanced gastric cancer tissues. Identification of sTn carrier proteins will help understand mechanisms of metastatic phenotype acquisition of gastric cancer cells by ST6GalNAcI and sTn.

Show MeSH
Related in: MedlinePlus