The Role of Brevican in Glioma: Promoting Tumor Cell Motility in Vitro and in Vivo

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2012 Dec 21

PMID 23253190

Citations 25

Authors

Renquan Lu

Chengsheng Wu

Lin Guo

Yingchao Liu

Wei Mo

Huijie Wang

Jianbo Ding

Eric T Wong

Min Yu

Affiliations

Soon will be listed here.

Abstract

Background: Malignant glioma is a common primary tumor of the central nervous system. Brevican, an abundant extracellular matrix component in the adult brain, plays a critical role in the process of glioma. The mechanisms for the highly invasive behavior of gliomas are still poorly understood. The aim of this study was to examine whether brevican is a predictor of glioma and its roles in glioma cell motility.

Methods: In this study, immunohistochemistry staining for brevican expression was performed in malignant gliomas and benign controls. We also explored the effects of brevican on cell adhesion and migration in brevican-overexpressed cells. Knockdown of brevican expression was achieved by stable transfection of U251 cells transduced with a construct encoding a short hairpin DNA directed against the brevican gene, which correspondingly, down-regulated the proliferation, invasion and spread of brevican-expressing cells. Moreover, the role of brevican in the growth and progression of glioma was demonstrated by in vivo studies.

Results: Our results provide evidence for the molecular and cellular mechanisms that may underlie the motility-promoting role of brevican in the progression of glioma. The role of brevican as a target for immunotherapy might be taken into consideration in future studies.

Conclusions: This study suggests that expression of brevican is associated with glioma cell adhesion, motility and tumor growth, and also is related to glioma cell differentiation, therefore it may be a marker for malignance degree of glioma.

Citing Articles

O-GalNAc glycans are enriched in neuronal tracts and regulate nodes of Ranvier.

Noel M, Suttapitugsakul S, Cummings R, Mealer R Proc Natl Acad Sci U S A. 2025; 122(9):e2418949122.

PMID: 39999163 PMC: 11892645. DOI: 10.1073/pnas.2418949122.

Gene expression and immunohistochemistry analysis of ADAMTS-1 and its substrates in odontogenic keratocyst.

de Souza Neto O, de Moraes A, Fuzii H, Maneschy Faria A, Freitas V, da Silva Kataoka M Diagn Pathol. 2025; 20(1):1.

PMID: 39762885 PMC: 11705738. DOI: 10.1186/s13000-024-01576-0.

Biomimetic Hyaluronan Binding Biomaterials to Capture the Complex Regulation of Hyaluronan in Tissue Development and Function.

Huffer A, Mao M, Ballard K, Ozdemir T Biomimetics (Basel). 2024; 9(8).

PMID: 39194478 PMC: 11351607. DOI: 10.3390/biomimetics9080499.

Distinguishing glioblastoma progression from treatment-related changes using DTI directionality growth analysis.

van den Elshout R, Ariens B, Esmaeili M, Akkurt B, Mannil M, Meijer F Neuroradiology. 2024; 66(12):2143-2151.

PMID: 39153088 PMC: 11611950. DOI: 10.1007/s00234-024-03450-8.

Hyaluronic Acid Interacting Molecules Mediated Crosstalk between Cancer Cells and Microenvironment from Primary Tumour to Distant Metastasis.

Xu Y, Benedikt J, Ye L Cancers (Basel). 2024; 16(10).

PMID: 38791985 PMC: 11119954. DOI: 10.3390/cancers16101907.

References

Seidenbecher C, Richter K, Rauch U, Fassler R, Garner C, Gundelfinger E . Brevican, a chondroitin sulfate proteoglycan of rat brain, occurs as secreted and cell surface glycosylphosphatidylinositol-anchored isoforms. J Biol Chem. 1995; 270(45):27206-12. DOI: 10.1074/jbc.270.45.27206. View

Lettau I, Hattermann K, Held-Feindt J, Brauer R, Sedlacek R, Mentlein R . Matrix metalloproteinase-19 is highly expressed in astroglial tumors and promotes invasion of glioma cells. J Neuropathol Exp Neurol. 2010; 69(3):215-23. DOI: 10.1097/NEN.0b013e3181ce9f67. View

Yamaguchi Y . Lecticans: organizers of the brain extracellular matrix. Cell Mol Life Sci. 2000; 57(2):276-89. PMC: 11146776. DOI: 10.1007/PL00000690. View

Cattaruzza S, Perris R . Proteoglycan control of cell movement during wound healing and cancer spreading. Matrix Biol. 2005; 24(6):400-17. DOI: 10.1016/j.matbio.2005.06.005. View

Hu B, Kong L, Matthews R, Viapiano M . The proteoglycan brevican binds to fibronectin after proteolytic cleavage and promotes glioma cell motility. J Biol Chem. 2008; 283(36):24848-59. PMC: 3259830. DOI: 10.1074/jbc.M801433200. View

Lu R, Sun M, Feng J, Gao X, Guo L . Myofibrillogenesis regulator 1 (MR-1) is a novel biomarker and potential therapeutic target for human ovarian cancer. BMC Cancer. 2011; 11:270. PMC: 3132198. DOI: 10.1186/1471-2407-11-270. View

Goldbrunner R, Bernstein J, Tonn J . Cell-extracellular matrix interaction in glioma invasion. Acta Neurochir (Wien). 1999; 141(3):295-305; discussion 304-5. DOI: 10.1007/s007010050301. View

Norden A, Young G, Setayesh K, Muzikansky A, Klufas R, Ross G . Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology. 2008; 70(10):779-87. DOI: 10.1212/01.wnl.0000304121.57857.38. View

Bolteus A, Berens M, Pilkington G . Migration and invasion in brain neoplasms. Curr Neurol Neurosci Rep. 2002; 1(3):225-32. DOI: 10.1007/s11910-001-0022-x. View

10.

Viapiano M, Matthews R, Hockfield S . A novel membrane-associated glycovariant of BEHAB/brevican is up-regulated during rat brain development and in a rat model of invasive glioma. J Biol Chem. 2003; 278(35):33239-47. DOI: 10.1074/jbc.M303480200. View

11.

Zhang H, Kelly G, Zerillo C, Jaworski D, Hockfield S . Expression of a cleaved brain-specific extracellular matrix protein mediates glioma cell invasion In vivo. J Neurosci. 1998; 18(7):2370-6. PMC: 6793111. View

12.

Nutt C, Matthews R, Hockfield S . Glial tumor invasion: a role for the upregulation and cleavage of BEHAB/brevican. Neuroscientist. 2001; 7(2):113-22. DOI: 10.1177/107385840100700206. View

13.

Jaworski D, Kelly G, Hockfield S . BEHAB, a new member of the proteoglycan tandem repeat family of hyaluronan-binding proteins that is restricted to the brain. J Cell Biol. 1994; 125(2):495-509. PMC: 2120027. DOI: 10.1083/jcb.125.2.495. View

14.

Yamaguchi Y . Brevican: a major proteoglycan in adult brain. Perspect Dev Neurobiol. 1996; 3(4):307-17. View

15.

Jaworski D, Kelly G, Piepmeier J, Hockfield S . BEHAB (brain enriched hyaluronan binding) is expressed in surgical samples of glioma and in intracranial grafts of invasive glioma cell lines. Cancer Res. 1996; 56(10):2293-8. View

16.

Iwamoto F, Abrey L, Beal K, Gutin P, Rosenblum M, Reuter V . Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma. Neurology. 2009; 73(15):1200-6. PMC: 2839807. DOI: 10.1212/WNL.0b013e3181bc0184. View

17.

Viapiano M, Bi W, Piepmeier J, Hockfield S, Matthews R . Novel tumor-specific isoforms of BEHAB/brevican identified in human malignant gliomas. Cancer Res. 2005; 65(15):6726-33. DOI: 10.1158/0008-5472.CAN-05-0585. View

18.

Rauch U, Meyer H, Brakebusch C, Seidenbecher C, Gundelfinger E, Beier D . Sequence and chromosomal localization of the mouse brevican gene. Genomics. 1997; 44(1):15-21. DOI: 10.1006/geno.1997.4853. View

19.

Subramanian A, Harris A, Piggott K, Shieff C, Bradford R . Metastasis to and from the central nervous system--the 'relatively protected site'. Lancet Oncol. 2002; 3(8):498-507. DOI: 10.1016/s1470-2045(02)00819-7. View

20.

Nutt C, Zerillo C, Kelly G, Hockfield S . Brain enriched hyaluronan binding (BEHAB)/brevican increases aggressiveness of CNS-1 gliomas in Lewis rats. Cancer Res. 2001; 61(19):7056-9. View