Altered arginine metabolism in colon cancer: a sign of increased proliferative potential of tumor-adjacent tissue

Branko  Branković; Goran Stanojević; Andrej Veljković; Gordana Kocić; Milica Nestorović; Boris Đinđić; Jelena Bašić; Ivana Stojanović

doi:10.2298/ABS220531023B

Authors

Branko Branković 1. University of Niš, Faculty of Medicine, 18000 Niš, Serbia; 2. University Clinical Center Niš, Clinic for Surgery, 18000 Niš, Serbia https://orcid.org/0000-0003-1258-9126
Goran Stanojević 1. University of Niš, Faculty of Medicine, 18000 Niš, Serbia; 2. University Clinical Center Niš, Clinic for Surgery, 18000 Niš, Serbia https://orcid.org/0000-0001-9401-7097
Andrej Veljković University of Niš, Faculty of Medicine, Department of Biochemistry, 18000 Niš, Serbia https://orcid.org/0000-0001-5950-7517
Gordana Kocić University of Niš, Faculty of Medicine, Department of Biochemistry, 18000 Niš, Serbia https://orcid.org/0000-0003-2386-2466
Milica Nestorović 1. University of Niš, Faculty of Medicine, 18000 Niš, Serbia; 2. University Clinical Center Niš, Clinic for Surgery, 18000 Niš, Serbia https://orcid.org/0000-0003-4776-879X
Boris Đinđić University of Niš, Faculty of Medicine, Department of Pathophysiology, 18000 Niš, Serbia https://orcid.org/0000-0002-6772-2986
Jelena Bašić University of Niš, Faculty of Medicine, Department of Biochemistry, 18000 Niš, Serbia https://orcid.org/0000-0002-9221-561X
Ivana Stojanović University of Niš, Faculty of Medicine, Department of Biochemistry, 18000 Niš, Serbia https://orcid.org/0000-0002-8835-9370

DOI:

https://doi.org/10.2298/ABS220531023B

Keywords:

colon cancer, arginine, arginase, polyamines, nitric oxide

Abstract

Paper description:

Arginine metabolite levels and arginase activity in colon cancer tumors and adjacent tissues could have a predictive value in risk assessment for tumor growth and patient survival after surgery.
Arginine metabolite concentrations and arginase activity were determined in colon cancer tumors and adjacent and healthy tissues post-surgery and linked to patient survival.
Polyamine concentrations and arginase activity was significantly increased in cancer and adjacent tissues, indicating a high proliferative potential of tissue surrounding the tumor.
This study provides a basis for understanding the possible predictive value of arginase activity in adjacent tumor tissue for its proliferative potential.

Abstract: Colorectal cancer (CRC) is one of the most frequent forms of malignant tumors in the human population. The literature data about the role of arginine metabolism in CRC point out its double-faced role. In three tissue specimens of 50 patients who underwent surgical resection for colon adenocarcinoma (tumor, adjacent and healthy tissues more than 10 cm from the tumor border – at the incision margin) taken during surgery, polyamines and the concentration of NO₂+NO₃and arginase activity were determined. Polyamine levels and arginase activity were significantly increased in cancer and adjacent tissue specimens compared to healthy ones, while the level of NO₂+NO₃ was significantly lower in cancer compared to both adjacent and healthy tissues. The high polyamine content in the adjacent colonic mucosa indicates a high proliferative potential of tumor-adjacent tissue. Although we found individual correlations indicating the possible prognostic value of arginase, the performed statistical analysis did not show a predictive significance of arginase activity in the examined tissue specimens for five-year survival of the patients. Nevertheless, the obtained results provide the rationale for further studies of arginine metabolism in tissue specimens after surgery in patients with CRC, which could be useful in the evaluation of the risk for tumor growth, recurrence, metastases and survival after surgical intervention.

Downloads

Download data is not yet available.

References

Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383:1490-502. https://doi.org/10.1016/S0140-6736(13)61649-9

Denkert C, Budczies J, Weichert W, Wohlgemuth G, Scholz M, Kind T. Metabolite profiling of human colon carcinoma-deregulation of TCA cycle and amino acid turnover. Mol Cancer. 2008;7:72. https://doi.org/10.1186/1476-4598-7-72

Martinez ME, O'Brien TG, Fultz KE, Babbar N, Yerushalmi H, Qu N. Pronounced reduction in adenoma recurrence associated with aspirin use and a polymorphism in the ornithine decarboxylase gene. Proc Natl Acad Sci USA. 2003;100(13):7859-64. https://doi.org/10.1073/pnas.1332465100

Kingsnorth AN, Lumsden AB, Wallace HM. Polyamines in colorectal cancer. Br J Surg. 1984;71:791-4. https://doi.org/10.1002/bjs.1800711019

Casero RA, Murray Jr, Stewart T, Pegg AE. Polyamine metabolism and cancer: Treatments, challenges, and opportunities. Nat Rev Cancer. 2018;18:681-95. https://doi.org/10.1038/s41568-018-0050-3

Choi Y, Oh ST, Won MA, Choi KM, Ko MJ, Seo D, Jeon TW, Baik IH, Ye SK, Park KU, Park IC, Jang BC, Seo JY, Lee YH. Targeting ODC1 inhibits tumor growth through reduction of lipid metabolism in human hepatocellular carcinoma. Biochem Biophys Res Commun. 2016;478:1674-81. https://doi.org/10.1016/j.bbrc.2016.09.002

Iyer R, Jenkinson CI, Vockley JG, Keru RM, Groody WV, Cederbaum S. Human arginases and arginase deficiency. J Inherit Met Dis. 1998;21(Suppl.1):86-100. https://doi.org/10.1023/A:1005313809037

Rath M, Müller I, Kropf P, Closs EI, Munder M. Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages. Front Immunol. 2014;5:532. https://doi.org/10.3389/fimmu.2014.00532

Pan M, Choudry HA, Epler Mj, Meng QH, Karinch A, Lin CM, Souba W. Arginine Transport in Catabolic Disease States. J Nutr 2004;34(10):2826S-2829S. https://doi.org/10.1093/jn/134.10.2826S

Du T, Han J. Arginine Metabolism and Its Potential in Treatment of Colorectal Cancer. Front Cell Dev Biol. 2021;658861. https://doi.org/10.3389/fcell.2021.658861

Jahani M, Noroznezhad F, Mansouri K. Arginine: Challenges and opportunities of this two-faced molecule in cancer therapy. Biomed Pharmacother. 2018;102:594-601. https://doi.org/10.1016/j.biopha.2018.02.109

Hu Y, Xiang J, Su L, Tang X. The regulation of nitric oxide in tumor progression and therapy. J Int Med Res. 2020;48(2):0300060520905985. https://doi.org/10.1177/0300060520905985

Lechner M, Lirk P, Rieder, J. Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin. Semin Cancer Biol. 2005;15:277-89. https://doi.org/10.1016/j.semcancer.2005.04.004

Mota MBS, Carvalho MA, Monteiro ANA, Mesquita RD. DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens. Parasites Vectors. 2019;12:533. https://doi.org/10.1186/s13071-019-3792-1

Khan FH, Dervan E, Bhattacharyya DD, McAuliffe JD, Miranda KM, Glynn SA. The Role of Nitric Oxide in Cancer: Master Regulator or NOt? Int J Mol Sci. 2020;21(24):9393. https://doi.org/10.3390/ijms21249393

Morbidelli L, Donnini S, Ziche M. Role of nitric oxide in tumor angiogenesis. Cancer Treat Res. 2004;117:155-67. https://doi.org/10.1007/978-1-4419-8871-3_11

Swayden M, Bekdash A, Fakhoury I, l-Atat O, Borjac-Natour JA, El-Sibai M, Abi-Habib RJ. Activation of autophagy following [HuArgI (Co)-PEG5000]-induced arginine deprivation mediates cell death in colon cancer cells. Human Cell. 2021;34:152-64. https://doi.org/10.1007/s13577-020-00437-4

Ekegren T, Gomes-Trolinb C. Determination of polyamines in human tissues by precolumn derivatization with 9-Xuorenylmethyl chloroformate and high-performance liquid chromatography. Analyt Biochem. 2005;338:179-85. https://doi.org/10.1016/j.ab.2004.11.040

Navaro-Gonzalvez JA, Garcia-Benayas C, Arenas J. Semiautomated measurement of nitrate in biological fluids. Clin Chem. 1998;44:679-81. https://doi.org/10.1093/clinchem/44.3.679

Porembska Z, Kedra M. Early diagnosis of myocardial infarction by arginase activity determination. Clin Chim Acta. 1975;60:355-61. https://doi.org/10.1016/0009-8981(75)90078-9

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin phenol reagent. J Biol Chem. 1951;193:265-75. https://doi.org/10.1016/S0021-9258(19)52451-6

Stojanović I, Veljković A, Branković B, Pavlović D, Stanojević G, Kocić G, Janošević P, Nestorović M, Petrović D. Polyamine and nitric oxide interactions in colorectal cancers. In: Proceedings of the Oxidative stress and cancerogenesis: diagnostic and therapeutic possibilities. Nis, Serbia; 2012. p. 45-53.

Brankovic B, Stanojevic G, Stojanovic I, Veljkovic A, Kocic G, Janosevic P, Nestorovic M, Petrovic D. Djindjic B, Pavlovic D, Krivokapic, Z. Nitric oxide synthesis modulation - a possible diagnostic and therapeutic target in colorectal cancer. JBUON. 2017;22(1):162-69.

Janež J, Škapin AD. Comparison of a Five-Year Survival and Cancer Recurrence between Laparoscopically Assisted and Open Colonic Resections due to Adenocarcinoma - A Single Centre Experience. Medicina. 2020;56:93. https://doi.org/10.3390/medicina56020093

Lind DS. Arginine and Cancer. Am Soc Nutr Sci. 2004;134(10 Suppl): 2837S-2841S. https://doi.org/10.1093/jn/134.10.2837S

Cao Y, Feng Y, Zhang Y, Zhu X, Jin F. L-Arginine supplementation inhibits the growth of breast cancer by enhancing innate and adaptive immune responses mediated by suppression of MDSCs in vivo. BMC Cancer. 2016;16(1):343. https://doi.org/10.1186/s12885-016-2376-0

Fultang L, Vardon A, De Santo C, Mussai F. Molecular basis and current strategies of therapeutic arginine depletion for cancer. Int J Cancer. 2016;139:501-9. https://doi.org/10.1002/ijc.30051

Chen CL, Hsu SC, Ann DK, Yen Y, Kung HJ. Arginine Signaling and Cancer Metabolism. Cancers (Basel) 2021;13(14):3541. https://doi.org/10.3390/cancers13143541

Karimian J, Hadi A, Salehi-sahlabadi A, Kafeshan M. The Effect of Arginine Intake on Colorectal Cancer: a Systematic Review of Literatures. Clin Nutr Res. 2019;8(3):209-18. https://doi.org/10.7762/cnr.2019.8.3.209

Scalabrino G, Lorenzini EC. Polyamines and mammalian hormones. Part II: Paracrine signals and intracellular regulators. Mol Cell Endocrinol. 1991;77(1-3):37-56. https://doi.org/10.1016/0303-7207(91)90057-Y

Ignatenko NA, Gerner EW, Besselsen DG. Defining the role of polyamines in colon carcinogenesis using mouse models. J Carcinog 2011;10:1-10. https://doi.org/10.4103/1477-3163.79673

Singh R, Pervin S, Karimi A, Cederbaum S, Chaudhuri G. Arginase activity in human breast cancer cell lines: N(omega)-hydroxy-L- arginine selectively inhibits cell proliferation and induces apoptosis in MDA-MB-468 cells. Cancer Res. 2000;60:3305-12.

Naso P, Lanteri R, Acquaviva R, Licata F, Bonanno G, Licata A. Polyamines levels in colorectal cancer: new markers? Hepatogastroenterology. 2005;52(62):433-6.

Tse RT, Wong CY, Ka-Fung Chiu P, Ng CF. The Potential Role of Spermine and Its Acetylated Derivative in Human Malignancies. Int J Mol Sci. 2022;23(3):1258. https://doi.org/10.3390/ijms23031258

Tsujinaka S, Soda K, Kano Y, Konishi F. Spermine accelerates hypoxia-initiated cancer cell migration. Int J Oncol. 2011:38(2):305-12. https://doi.org/10.3892/ijo.2010.849

Munder M. Arginase: an emerging key player in the mammalian immune system. Br J Pharmacol. 2009;158:638-51. https://doi.org/10.1111/j.1476-5381.2009.00291.x

Bedoya AM, Tate DJ, Baena A, Córdoba CM, Borrero M, Pareja R, Rojas F, Patterson JR, Herrero R, Zea AH. Immunosuppression in cervical cancer with special reference to arginase activity. Gynecol Oncol, 2014;135:74-80. https://doi.org/10.1016/j.ygyno.2014.07.096

Radwan NA, Ahmed NS. The diagnostic value of arginase-1 immunostaining in differentiating hepatocellular carcinoma from metastatic carcinoma and cholangiocarcinoma as compared to HepPar-1. Diagn Pathol. 2012;7:149. https://doi.org/10.1186/1746-1596-7-149

Cederbaum SD, Yu H, Grody WW, Kern RM, Yoo P, Iyerd RK. Arginases I and II: do their functions overlap? Mol Genet Metab. 2004;81:S38-S39. https://doi.org/10.1016/j.ymgme.2003.10.012

Ma Z, Liana J, Yang M, Wuyang J, Zhao C, Chen W, Kiu C, Zhao Q, Lou C, Hang J, Zhang Y. Overexpression of Arginase-1 is an indicator of poor prognosis in patients with colorectal cancer. Pathol Res Pract. 2019;215(6):152383. https://doi.org/10.1016/j.prp.2019.03.012

Zou S, Wang X, Liua P, Kea C, Xu S. Arginine metabolism and deprivation in cancer therapy. Biomed Pharmacother. 2019;118:109210. https://doi.org/10.1016/j.biopha.2019.109210

Altered arginine metabolism in colon cancer: a sign of increased proliferative potential of tumor-adjacent tissue

Authors

DOI:

Keywords:

Abstract

Downloads

References

Downloads

Published

How to Cite

Issue

Section

License

Most read articles by the same author(s)

Current Issue

Make a Submission