Immunohistochemical study of arginase in cancer of the stomach

Wu, Chew Wun; Chung, Wen Wei; W, C; Kao, Hung Wen; Lui, Wing Yiu; P’eng, Fang-Ku; Wang, S R

doi:10.1007/bf00202199

Cited by 26 publications

(17 citation statements)

References 15 publications

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“…ASE I is also produced by several tumors including gastric, colon, breast, and lung cancers (42)(43)(44)(45)(46). Most reports have associated the increased ASE expression by tumor cells with the need to produce polyamines to sustain the rapid malignant cell proliferation (29).…”

Section: Discussionmentioning

confidence: 99%

l-Arginine Consumption by Macrophages Modulates the Expression of CD3ζ Chain in T Lymphocytes

Rodríguez

Zea

DeSalvo

et al. 2003

The Journal of Immunology

428

355

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l-Arginine plays a central role in the normal function of several organs including the immune system. It is metabolized in macrophages by inducible nitric oxide synthase to produce nitric oxide, important in the cytotoxic mechanisms, and by arginase I (ASE I) and arginase II (ASE II) to synthesize l-ornithine and urea, the first being the precursor for the production of polyamines needed for cell proliferation. l-Arginine availability can modulate T cell function. Human T cells stimulated and cultured in the absence of l-arginine lose the expression of the TCR ζ-chain (CD3ζ) and have an impaired proliferation and a decreased cytokine production. The aim of this work was to test whether activated macrophages could modulate extracellular levels of l-arginine and alter T cell function, and to determine which metabolic pathway was responsible for this event. The results show that macrophages stimulated with IL-4 + IL-13 up-regulate ASE I and cationic amino acid transporter 2B, causing a rapid reduction of extracellular levels of l-arginine and inducing decreased expression of CD3ζ and diminished proliferation in normal T lymphocytes. Competitive inhibitors of ASE I or the addition of excess l-arginine lead to the re-expression of CD3ζ and recovery of T cell proliferation. In contrast, inducible nitric oxide synthase or ASE II failed to significantly reduce the extracellular levels of l-arginine and modulate CD3ζ expression. These results may provide new insights into the mechanisms leading to T cell dysfunction and the down-regulation of CD3ζ in cancer and chronic infectious diseases.

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Section: Discussionmentioning

confidence: 99%

l-Arginine Consumption by Macrophages Modulates the Expression of CD3ζ Chain in T Lymphocytes

Rodríguez

Zea

DeSalvo

et al. 2003

The Journal of Immunology

428

355

View full text Add to dashboard Cite

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“…Arginase II has been reported to be overexpressed in cancerous tissues in general (Harris et al, 1983;Leu and Wang, 1992;Suer Gokmen et al, 1999;del Ara et al, 2002;Porembska et al, 2003) and it is well established that this gene is overexpressed in gastric adenocarcinomas (Wu et al, 1996). Since ARG2 catalyses the conversion of arginine to ornithine, a crucial metabolite in biosynthesis of glutamic acid, proline and polyamines (Vockley et al, 1996), an increase in the level of arginase may reflect accelerated metabolism due to cell proliferation or tumour growth.…”

Section: Discussionmentioning

confidence: 99%

Differential gene-expression profiles associated with gastric adenoma

et al. 2004

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Gastric adenomas may eventually progress to adenocarcinomas at varying rates. The purpose of the present study was to identify gene-expression profiles linked to the heterogeneous nature of gastric adenoma as compared to adenocarcinoma. Suppression subtractive hybridisation analysis was performed to extract relevant genes from two cases of low-and high-grade gastric adenomas. The identified genes were quantified by RT -PCR in 14 low-grade adenoma, nine high-grade adenoma and nine adenocarcinoma samples, followed by hierarchical clustering analysis to separate tumours into groups according to their gene-expression profiles. Nine genes previously implicated in carcinogenesis in a variety of organs, including three genes related to gastric adenocarcinoma, were identified. The overexpression of these genes in gastric adenoma has not been reported previously. The clustering analysis of these nine genes across 32 cases identified three groups, one of which consisted primarily of adenocarcinomas, whereas the other two groups consisted of adenomas. One group of adenomas, characterised by larger tumour size, exhibited gene-expression profiles of an intestinal cell lineage implicated in the pathogenesis of an intestinal-type gastric adenocarcinoma. Another adenoma group consisting of low-grade adenomas with smaller tumour size exhibited a unique expression profile. In conclusion, clustering analysis of expression profiles using a limited number of genes may serve as molecular markers for gastric adenoma with different biological properties. Although the prognostic values of these gene-expression profiles need to be evaluated in further follow-up study of adenoma cases, these findings add new insights to (a) our understanding of the pathogenesis of gastric tumours, (b) the development of specific tumour markers for clinical practice, and (c) the design of novel therapeutic targets.

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“…Arginase has been found at increased levels in the serum and cancer tissue of cancer patients, such as gastric cancer [1,2], colorectal cancer [3,4], breast cancer [5], skin cancer [6], lung cancer [7,8], prostate cancer [9], etc. The presence of these increased levels of arginase in cancer tissue may promote cell proliferation [10,11] through the action of polyamines [11] formed from ornithine.…”

Section: Introductionmentioning

confidence: 99%