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¹H NMR based serum metabolic profiles associated with pathological progression of pancreatic islet β cell tumor in Rip1-Tag2 mice.

Yang Y, Liu Y, Zheng L, Zhang Q, Gu Q, Wang L, Wang L - Int. J. Biol. Sci. (2015)

Bottom Line: Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells.In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism.The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Basic Course, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China ; 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.

ABSTRACT
Pancreatic islet β cell tumor is the most common islet cell tumor. A well-characterized tumor progression in Rip1-Tag2 mice undergoes five stages, involving normal, hyperplasia, angiogenic islets, tumorigenesis and invasive carcinoma. (1)H NMR based metabonomics was applied to identify potential biomarkers for monitoring pancreatic islet β cell tumor progression in Rip1-Tag2 mice. Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells. At angiogenic islets stage, the up-regulated glycolysis, disturbed choline and phospholipid metabolism composed the metabolic signature. In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism. All the changes were aggravated at invasive carcinoma stage, coupled with notable changes in alanine, glutamate and glycine. Moreover, the distinct metabolic phenotype was found associated with the implanting of SV40 large T antigen in Rip1-Tag2 mice. The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

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Representative images of HE stainings of pancreatic and tumor tissues from Rip1-Tag2 mice at different stages (3, 5, 8, 10 and 14 weeks).
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Figure 1: Representative images of HE stainings of pancreatic and tumor tissues from Rip1-Tag2 mice at different stages (3, 5, 8, 10 and 14 weeks).

Mentions: Fig. 1 showed a progressively histopathological assessment in Rip1-Tag2 mice. It was found that proliferation of pancreatic islet β cells started at about 5 weeks with distinctly accumulated islet cells and enlarged volume compared to the morphological feature at 3 weeks. At about 8 weeks, angiogenic islets characterized by endothelial proliferation, vascular dilation, and microhemorrhagin was prevalent and then solid tumors emerged after soon. From the morphological feature at 10 weeks, we can find that the tumors were encapsulated and clear boundary from the surrounding tissue appeared, with a little tendency of microinvasion. Up to 14 weeks, invasive carcinoma commonly appeared in features of obvious atypia of islet structure and invasiveness with surrounding tissue. And both of tumor and invasive carcinoma were intensively vascularized by dilated blood vessels.


¹H NMR based serum metabolic profiles associated with pathological progression of pancreatic islet β cell tumor in Rip1-Tag2 mice.

Yang Y, Liu Y, Zheng L, Zhang Q, Gu Q, Wang L, Wang L - Int. J. Biol. Sci. (2015)

Representative images of HE stainings of pancreatic and tumor tissues from Rip1-Tag2 mice at different stages (3, 5, 8, 10 and 14 weeks).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4400390&req=5

Figure 1: Representative images of HE stainings of pancreatic and tumor tissues from Rip1-Tag2 mice at different stages (3, 5, 8, 10 and 14 weeks).
Mentions: Fig. 1 showed a progressively histopathological assessment in Rip1-Tag2 mice. It was found that proliferation of pancreatic islet β cells started at about 5 weeks with distinctly accumulated islet cells and enlarged volume compared to the morphological feature at 3 weeks. At about 8 weeks, angiogenic islets characterized by endothelial proliferation, vascular dilation, and microhemorrhagin was prevalent and then solid tumors emerged after soon. From the morphological feature at 10 weeks, we can find that the tumors were encapsulated and clear boundary from the surrounding tissue appeared, with a little tendency of microinvasion. Up to 14 weeks, invasive carcinoma commonly appeared in features of obvious atypia of islet structure and invasiveness with surrounding tissue. And both of tumor and invasive carcinoma were intensively vascularized by dilated blood vessels.

Bottom Line: Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells.In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism.The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

View Article: PubMed Central - PubMed

Affiliation: 1. School of Basic Course, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China ; 2. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, 510006, PR China.

ABSTRACT
Pancreatic islet β cell tumor is the most common islet cell tumor. A well-characterized tumor progression in Rip1-Tag2 mice undergoes five stages, involving normal, hyperplasia, angiogenic islets, tumorigenesis and invasive carcinoma. (1)H NMR based metabonomics was applied to identify potential biomarkers for monitoring pancreatic islet β cell tumor progression in Rip1-Tag2 mice. Multivariate analysis results showed the serum metabonome at hyperplasia stage shared the similar characteristics with the ones at normal stage as a result of slight proliferation of pancreatic islet β cells. At angiogenic islets stage, the up-regulated glycolysis, disturbed choline and phospholipid metabolism composed the metabolic signature. In addition to the changes mentioned above, several metabolites were identified as early biomarkers for tumorigenesis, including increased methionine, citrate and choline, and reduced acetate, taurine and glucose, which suggested the activated energy and amino acid metabolism. All the changes were aggravated at invasive carcinoma stage, coupled with notable changes in alanine, glutamate and glycine. Moreover, the distinct metabolic phenotype was found associated with the implanting of SV40 large T antigen in Rip1-Tag2 mice. The combined metabolic and multivariate statistics approach provides a robust method for screening the biomarkers of disease progression and examining the association between gene and metabolism.

Show MeSH
Related in: MedlinePlus