l-Arginine as a factor increasing arginase significance in diagnosis of primary and metastatic colorectal cancer

Graboń, Wojciech; Mielczarek-Puta, Magdalena; Chrzanowska, Alicja; Barańczyk‐Kuźma, Anna

doi:10.1016/j.clinbiochem.2008.11.018

Cited by 22 publications

(14 citation statements)

References 29 publications

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“…Perioperative arginine-enriched nutrition significantly improved the long-term overall survival and long-term disease-specific survival in malnourished patients with head and neck cancer (Buijs et al, 2010). Higher expression and activity of ARG1 are often observed in the blood of cancer patients (Polat et al, 2003;Grabon et al, 2009;Rodriguez et al, 2009). After surgical removal of malignant tumors, remnant cells can proliferate.…”

Section: Discussionmentioning

confidence: 99%

Modulation of L-Arginine-Arginase Metabolic Pathway Enzymes: Immunocytochemistry and mRNA Expression in Peripheral Blood and Tissue Levels in Head and Neck Squamous Cell Carcinomas in North East India

Srivastava

Ghosh²

2015

Asian Pacific Journal of Cancer Prevention

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Background: Arginine may play important roles in tumor progression by providing ornithine for polyamine biosynthesis, required for cell growth. The aim of this work was to determine the expression of arginine metabolic pathway enzymes in head and neck squamous cell carcinoma (HNSCC) in northeast India. Materials and Methods: The expressions of arginase isoforms (ARG1 and ARG2), ornithine aminotransferase (OAT) and ornithine decarboxylase (ODC) were examined in fifty paired HNSCC and adjacent non-tumor tissues by immunohistochemistry. Immunocytochemistry, semiquantitative reverse transcription sq-PCR and quantitative real-time qPCR were used to assess protein and mRNA expressions in peripheral blood of fifty HNSCC patients and hundred controls. Results: ARG1 and ODC protein and mRNA were strongly expressed in peripheral blood from HNSCC patients. No ARG2 expression was observed. In vivo, expression of ARG1, ARG2 and ODC was significantly higher in tumor than in non-tumor tissues. Most tumors expressed low levels of OAT, with no difference in tissues or blood, compared to controls. The absolute extent of maximal ARG1 upregulation with qPCR showed 6.23 fold increase in HNSCC. Conclusions: These findings strongly suggest that in HNSCCs, the ARG1 pathway is stimulated leading to the formation of polyamines as indicated by higher ODC expression, which promote tumor growth.

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Section: Discussionmentioning

confidence: 99%

Modulation of L-Arginine-Arginase Metabolic Pathway Enzymes: Immunocytochemistry and mRNA Expression in Peripheral Blood and Tissue Levels in Head and Neck Squamous Cell Carcinomas in North East India

Srivastava

Ghosh²

2015

Asian Pacific Journal of Cancer Prevention

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“…L-arginine, a semi-essential amino acid, is a substrate for protein biosynthesis and a precursor for nitric oxide and polyamines, which play a crucial role in regulation of cell proliferation and differentiation[3]. Several studies showed that L-arginine was associated with for cancer development and progression[4–9], including colorectal cancer[10].…”

Section: Introductionmentioning

confidence: 99%

Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps

Sun

Zhu

Shrubsole

et al. 2017

The Journal of Nutritional Biochemistry

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Solute carrier family 7, member 2 (SLC7A2) gene encodes a protein called cationic amino acid transporter 2, which mediates the transport of arginine, lysine and ornithine. L-arginine is necessary for cancer development and progression, including an important role in colorectal cancer pathogenesis. Furthermore, previous studies found both calcium and magnesium inhibit the transport of arginine. Thus, calcium, magnesium or calcium:magnesium intake ratio may interact with polymorphisms in the SLC7A2 gene in associations with colorectal cancer. We conducted a two-phase case-control study within the Tennessee Colorectal Polyps Study. In the first phase, 23 tagging single-nucleotide polymorphisms (SNPs) in the SLC7A2 gene were included for 725 colorectal adenoma cases and 755 controls. In the second phase conducted in an independent set of 607 cases and 2113 controls, we replicated the significant findings in the first phase. We observed that rs2720574 significantly interacted with calcium:magnesium intake ratio in association with odds of adenoma, particularly multiple/advanced adenoma. In the combined analysis, among those with a calcium:magnesium intake ratio below 2.78, individuals who carried GC/CC genotypes demonstrated higher odds of adenoma OR (95% CI):1.36(1.11–1.68) and multiple/advanced adenoma OR (95% CI):1.68(1.28, 2.20) than those who carried the GG genotype. The P for interactions between calcium:magnesium intake ratio and rs2720574 were 0.002 for all adenoma and <0.001 for multiple/advanced adenoma. Among those with the GG genotype, a high calcium:magnesium ratio was associated with increased odds of colorectal adenoma OR (95%CI): 1.73(1.27–2.36) and advanced/multiple adenomas [1.62(1.05–2.50)]. Whereas, among those with the GC/CC genotypes, high calcium:magnesium ratio was related to reduced odds of colorectal adenoma [0.64(0.42–0.99)] and advanced/multiple adenomas [0.55(0.31–1.00)].

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“…Expression of ARG1 has frequently been described as an immunosuppressive mechanism employed by myeloid-derived suppressor cells (MDSC) as well as by M2-polarized and tumor-associated macrophages 7 . Furthermore, high expression and/or activity of ARG1 as well as reduced levels of L-Arg are often observed in the blood of cancer patients 8 - 11 …”

Section: Introductionmentioning

confidence: 99%

Expression patterns of the immunomodulatory enzyme arginase 1 in blood, lymph nodes and tumor tissue of early-stage breast cancer patients

et al. 2012

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Arginase 1 (ARG1) is an important enzyme in amino acid metabolism that also exerts immunoregulatory function. High ARG1 expression, which is associated with cell cycle arrest and functional unresponsiveness in T cells, has been observed after trauma, infections and in cancer patients. We studied ARG1 expression in early-stage breast cancer patients (stage 1, n = 20; stage 2, n = 23) by multi-parametric flow cytometry and immunohistochemistry. Despite a low tumor burden, ARG1 expression was significantly increased in blood-derived myeloid cells of breast cancer patients compared with healthy controls. The ARG1hi myeloid population in the blood of cancer patients contained a high frequency of CD14+ cells and was, therefore, distinct from the granulocytic ARG1+ population observed in control individuals. Expression of ARG1 in patient blood cells correlated with tumor grade and was significantly reduced after surgical tumor removal. ARG1+ myeloid cells could also be detected in tumors and tumor-draining lymph nodes, where ARG1 expression levels exceeded those measured in the blood. We conclude that even patients with early-stage breast cancer exhibit tumor-related changes of ARG1 expression. The level of ARG1-mediated immunomodulation at this early stage remains to be determined. However, high ARG1 expression is likely to interfere with antitumor T-cell responses and immunotherapeutic interventions, making ARG1 or its downstream effector interesting therapeutic targets.

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l-Arginine as a factor increasing arginase significance in diagnosis of primary and metastatic colorectal cancer

Cited by 22 publications

References 29 publications

Modulation of L-Arginine-Arginase Metabolic Pathway Enzymes: Immunocytochemistry and mRNA Expression in Peripheral Blood and Tissue Levels in Head and Neck Squamous Cell Carcinomas in North East India

Modulation of L-Arginine-Arginase Metabolic Pathway Enzymes: Immunocytochemistry and mRNA Expression in Peripheral Blood and Tissue Levels in Head and Neck Squamous Cell Carcinomas in North East India

Genetic variation in SLC7A2 interacts with calcium and magnesium intakes in modulating the risk of colorectal polyps

Expression patterns of the immunomodulatory enzyme arginase 1 in blood, lymph nodes and tumor tissue of early-stage breast cancer patients

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