Expression of Zonulin, C-kit, and Glial Fibrillary Acidic Protein in Human Gliomas

Overview

Journal Transl Oncol

Specialty Oncology

Date 2009 Aug 25

PMID 19701495

Citations 21

Authors

Marco Skardelly

Franz Paul Armbruster

Jurgen Meixensberger

Heidegard Hilbig

Affiliations

Soon will be listed here.

Abstract

The hallmarks of human malignant gliomas are their marked invasiveness and vascularity. Because angiogenesis and tumor invasion have been associated with extracellular matrix degradation and intercellular tight junctions, the involvement of zonulin in glioma biology is in the focus. We selected for histological examination five cases of glioblastoma WHO IV (nomenclature of the World Health Organization) and one case each from astrocytoma WHO III, meningioma WHO III, and meningioma WHO I as control samples. The meningioma WHO I is regarded as benign, whereas the meningioma WHO III is recognized as the transition form of malignant tumors in humans. The visualization of a newly designed antibody against human zonulin was studied in triple-labeling studies using fluorescence immunocytochemistry and compared with the expression of c-kit and glial fibrillary acidic protein in differently developed human gliomas. We found that increasing the expression of c-kit is accompanied by an increase of zonulin expression. Both are correlated to the degree of malignancy of human brain tumors. The expression of zonulin is correlated to the degradation of the blood-brain barrier as revealed by Griffonia simplicifolia lectin. In differently graded tumors, we found differently graded involvement of blood vessels in the tumor development, explaining patients' survival.

Citing Articles

A review of gut failure as a cause and consequence of critical illness.

Soranno D, Coopersmith C, Brinkworth J, Factora F, Muntean J, Mythen M Crit Care. 2025; 29(1):91.

PMID: 40011975 PMC: 11866815. DOI: 10.1186/s13054-025-05309-7.

From bench to bedside: an interdisciplinary journey through the gut-lung axis with insights into lung cancer and immunotherapy.

Dora D, Szocs E, Soos A, Halasy V, Somodi C, Mihucz A Front Immunol. 2024; 15:1434804.

PMID: 39301033 PMC: 11410641. DOI: 10.3389/fimmu.2024.1434804.

Zonulin as Gatekeeper in Gut-Brain Axis: Dysregulation in Glioblastoma.

Hagemeyer H, Hellwinkel O, Plata-Bello J Biomedicines. 2024; 12(8).

PMID: 39200114 PMC: 11352073. DOI: 10.3390/biomedicines12081649.

Evaluation of Zonulin Expression and Its Potential Clinical Significance in Glioblastoma.

Repossi R, Martin-Ramirez R, Gomez-Bernal F, Medina L, Farina-Jeronimo H, Gonzalez-Fernandez R Cancers (Basel). 2024; 16(2).

PMID: 38254845 PMC: 10814510. DOI: 10.3390/cancers16020356.

Hemorrhagic transformation in patients with large-artery atherosclerotic stroke is associated with the gut microbiota and lipopolysaccharide.

Huang Q, Wei M, Feng X, Luo Y, Liu Y, Xia J Neural Regen Res. 2023; 19(7):1532-1540.

PMID: 38051896 PMC: 10883505. DOI: 10.4103/1673-5374.385846.

References

Wang W, Uzzau S, Goldblum S, Fasano A . Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci. 2000; 113 Pt 24:4435-40. DOI: 10.1242/jcs.113.24.4435. View

Clemente M, De Virgiliis S, Kang J, Macatagney R, Musu M, Di Pierro M . Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function. Gut. 2003; 52(2):218-23. PMC: 1774976. DOI: 10.1136/gut.52.2.218. View

Cetin N, Dienel G, Gokden M . CD117 expression in glial tumors. J Neurooncol. 2005; 75(2):195-202. DOI: 10.1007/s11060-005-2318-1. View

Marinaro M, Fasano A, De Magistris M . Zonula occludens toxin acts as an adjuvant through different mucosal routes and induces protective immune responses. Infect Immun. 2003; 71(4):1897-902. PMC: 152047. DOI: 10.1128/IAI.71.4.1897-1902.2003. View

Sihto H, Tynninen O, Butzow R, Saarialho-Kere U, Joensuu H . Endothelial cell KIT expression in human tumours. J Pathol. 2007; 211(4):481-8. DOI: 10.1002/path.2125. View

Nakamura H, Takeshima H, Makino K, Kuratsu J . C-kit expression in germinoma: an immunohistochemistry-based study. J Neurooncol. 2005; 75(2):163-7. DOI: 10.1007/s11060-005-1593-1. View

Madara J . Loosening tight junctions. Lessons from the intestine. J Clin Invest. 1989; 83(4):1089-94. PMC: 303793. DOI: 10.1172/JCI113987. View

El Asmar R, Panigrahi P, Bamford P, Berti I, Not T, Coppa G . Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology. 2002; 123(5):1607-15. DOI: 10.1053/gast.2002.36578. View

Haberler C, Gelpi E, Marosi C, Rossler K, Birner P, Budka H . Immunohistochemical analysis of platelet-derived growth factor receptor-alpha, -beta, c-kit, c-abl, and arg proteins in glioblastoma: possible implications for patient selection for imatinib mesylate therapy. J Neurooncol. 2005; 76(2):105-9. DOI: 10.1007/s11060-005-4570-9. View

10.

Fasano A . Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Ann N Y Acad Sci. 2001; 915:214-22. DOI: 10.1111/j.1749-6632.2000.tb05244.x. View

11.

Madara J, Stafford J . Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers. J Clin Invest. 1989; 83(2):724-7. PMC: 303735. DOI: 10.1172/JCI113938. View

12.

Drago S, El Asmar R, Di Pierro M, Clemente M, Tripathi A, Sapone A . Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006; 41(4):408-19. DOI: 10.1080/00365520500235334. View

13.

Di Pierro M, Lu R, Uzzau S, Wang W, Margaretten K, Pazzani C . Zonula occludens toxin structure-function analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain. J Biol Chem. 2001; 276(22):19160-5. DOI: 10.1074/jbc.M009674200. View

14.

Mennel H, Hallier-Neelsen M, Hagner S, Benes L . Two novel cell specific receptor proteins, CRLR and CD 117 in human glial tumors. Clin Neuropathol. 2006; 25(3):107-14. View

15.

Catassi C, Fasano A . Celiac disease. Curr Opin Gastroenterol. 2009; 24(6):687-91. DOI: 10.1097/MOG.0b013e32830edc1e. View

16.

Sun L, Hui A, Su Q, Vortmeyer A, Kotliarov Y, Pastorino S . Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell. 2006; 9(4):287-300. DOI: 10.1016/j.ccr.2006.03.003. View