ABERRANT N-GLYCOSYLATION REGULATES INVASION OF MG-63 CELLS THROUGH EXTRACELLULAR MATRIX REMODELING

Authors

  • SARMILA HANIM MUSTAFA Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Institute of Medical and Molecular Biotechnology, Universiti Teknologi MARA, Cawangan Selangor, Kampus Sungai Buloh, 47000 Sungai Buloh, Selangor, Malaysia.
  • MUDIANA MUHAMAD Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA, Cawangan Selangor, Kampus Sungai Buloh, 47000 Sungai Buloh, Selangor, Malaysia.
  • SHARANIZA AB-RAHIM Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA, Cawangan Selangor, Kampus Sungai Buloh, 47000 Sungai Buloh, Selangor, Malaysia.

DOI:

https://doi.org/10.22159/ijap.2019.v11s5.T0053

Keywords:

Extracellular matrix genes, Glycosylation inhibitors, N-glycosylation, Osteosarcoma

Abstract

Objective: Despite advances in multimodal therapy, osteosarcoma (OS) still imposes big challenge due to its high rate of metastasis. The previous
studies reported that aberrant glycosylation in the cells mediates the invasion of several cancers including OS. However, its mechanism, particularly
N-glycosylation in OS progression, is still poorly understood. Thus, this study aims to investigate the effect of glycosylation inhibitions toward OS cells
invasiveness.
Materials and Methods: Both 1-deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (1-DMJ) were used to inhibit the activities of
alpha-glucosidase-I/II and alpha-1,2-mannosidase, respectively. Invasion assay and real-time polymerase chain reaction (PCR) (quantitative PCR
[qPCR]) analysis of extracellular matrix-related genes were performed at post 24 h of treatment with the inhibitors, 0.5 mM 1-DNJ and 0.5 mM 1-DMJ,
respectively, on the OS cell line, MG-63.
Results: Results showed that the inhibition of N-glycosylation with 1-DNJ decreases the invasion rate of MG-63 cells while the inhibition of
N-glycosylation by 1-DMJ caused the invasion rate of MG-63 cells to increase. qPCR analysis showed downregulated expression of matrix
metalloproteinase (MMP2) gene in both types of treatments while the expression of its inhibitor, tissue inhibitor of metalloproteinase (TIMP2) was
upregulated in both types of treatments. In this study, MMP9 genes were not detected in both samples; however, the expression of its inhibitor, TIMP1
was downregulated in MG-63 cells treated with 1-DNJ but upregulated in 1-DMJ treated cells.
Conclusion: It is concluded that 1-DNJ reduced the invasion rate in MG-63 cells through downregulation of MMP2 gene which subsequently reduced
degradation of collagen type IV. However, the contrasting effect showed by 1-DMJ requires further investigation to elucidate its underlying mechanism.

Downloads

Download data is not yet available.

References

1. Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival
rates from 1973 to 2004: Data from the surveillance, epidemiology, and
end results program. Cancer 2009;115:1531-43.
2. Evola FR, Costarella L, Pavone V, Caff G, Cannavò L, Sessa A, et al.
Biomarkers of osteosarcoma, chondrosarcoma, and Ewing sarcoma.
Front Pharmacol 2017;8:150.
3. Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Pediatr
Adolesc Osteosarcoma 2009;152:3-13.
4. Mirabello L, Troisi RJ, Savage SA. International osteosarcoma
incidence patterns in children and adolescents, middle ages and elderly
persons. Int J Cancer 2009;125:229-34.
5. Anderson ME. Update on survival in osteosarcoma. Orthop Clin North
Am 2016;47:283-92.
6. Haeger A, Wolf K, Zegers MM, Friedl P. Collective cell migration:
Guidance principles and hierarchies. Trends Cell Biol 2015;25:556-66.
7. Yan Z, Yin H, Wang R, Wu D, Sun W, Liu B, et al. Overexpression
of integrin-linked kinase (ILK) promotes migration and invasion of
colorectal cancer cells by inducing epithelial-mesenchymal transition
via NF-?B signaling. Acta Histochem 2014;116:527-33.
8. Canel M, Serrels A, Frame MC, Brunton VG. E-cadherin-integrin
crosstalk in cancer invasion and metastasis. J Cell Sci 2013;126:393-401.
9. Navab R, Strumpf D, To C, Pasko E, Kim KS, Park CJ, et al.
Integrin ?11?1 regulates cancer stromal stiffness and promotes
tumorigenicity and metastasis in non-small cell lung cancer. Oncogene
2016;35:1899-908.
10. de Leoz ML, Young LJ, An HJ, Kronewitter SR, Kim J, Miyamoto S, et al.
High-mannose glycans are elevated during breast cancer progression.
Mol Cell Proteomics 2011;10:M110.002717.
11. Alley WR Jr., Vasseur JA, Goetz JA, Svoboda M, Mann BF, Matei DE,
et al. N-linked glycan structures and their expressions change in the
blood sera of ovarian cancer patients. J Proteome Res 2012;11:2282-300.
12. Balmaña M, Giménez E, Puerta A, Llop E, Figueras J, Fort E,
et al. Increased ?1-3 fucosylation of ?-1-acid glycoprotein (AGP) in
pancreatic cancer. J Proteomics 2016;132:144-54.
13. Yeo HL, Fan TC, Lin RJ, Yu JC, Liao GS, Chen ES, et al. Sialylation of
vasorin by ST3Gal1 facilitates TGF-?1-mediated tumor angiogenesis
and progression. Int J Cancer 2019;144:1996-2007.
14. Zhu J, Xiong G, Fu H, Evers BM, Zhou BP, Xu R, et al. Chaperone
hsp47 drives malignant growth and invasion by modulating an ECM
gene network. Cancer Res 2015;75:1580-91.
15. Rohani MG, Parks WC. Matrix remodeling by MMPs during wound
repair. Matrix Biol 2015;44-46:113-21.
16. Clark AG, Vignjevic DM. Modes of cancer cell invasion and the role of
the microenvironment. Curr Opin Cell Biol 2015;36:13-22.
17. Pietruszewska W, Bojanowska-Po?niak K, Kobos J. Matrix
metalloproteinases MMP1, MMP2, MMP9 and their tissue
inhibitors TIMP1, TIMP2, TIMP3 in head and neck cancer: An
immunohistochemical study. Otolaryngol Pol 2016;70:32-43.
18. Oakes SA, Papa FR. The role of endoplasmic reticulum stress in human
pathology. Annu Rev Pathol 2015;10:173-94.
19. Wang M, Kaufman RJ. The impact of the endoplasmic reticulum
protein-folding environment on cancer development. Nat Rev Cancer
2014;14:581-97.
20. Kawano S, Hashimoto K, Miyama T, Goto S, Kanehisa M.
Prediction of glycan structures from gene expression data based on
glycosyltransferase reactions. Bioinformatics 2005;21:3976-82.
21. Tannous A, Pisoni GB, Hebert DN, Molinari M. N-linked sugarregulated
protein folding and quality control in the ER. Semin Cell Dev
Biol 2015;41:79-89.
22. Wang RJ, Yang CH, Hu ML 1-deoxynojirimycin inhibits metastasis
of B16F10 melanoma cells by attenuating the activity and expression
of matrix metalloproteinases-2 and -9 and altering cell surface
glycosylation. J Agric Food Chem 2010;58:8988-93.
23. Aebi M, Bernasconi R, Clerc S, Molinari M. N-glycan structures:
Recognition and processing in the ER. Trends Biochem Sci
2010;35:74-82.
24. Levanon SS, Aharonovitz O, Maor-Shoshani A, Abraham G, Kenett D,
Aloni Y. An efficient method to control high mannose and core fucose
levels in glycosylated antibody production using deoxymannojirimycin.
J Biotechnol 2018;276:54-62.
25. Liu J, Wen X, Liu B, Zhang Q, Zhang J, Miao H, et al. Diosmetin
inhibits the metastasis of hepatocellular carcinoma cells by
downregulating the expression levels of MMP-2 and MMP-9. Mol Med
Rep 2016;13:2401-8.
26. Webb AH, Gao BT, Goldsmith ZK, Irvine AS, Saleh N, Lee RP,
et al. Inhibition of MMP-2 and MMP-9 decreases cellular migration,
and angiogenesis in in vitro models of retinoblastoma. BMC Cancer
2017;17:434.
27. Zurac S, Neagu M, Constantin C, Cioplea M, Nedelcu R, Bastian A,
et al. Variations in the expression of TIMP1, TIMP2 and TIMP3 in
cutaneous melanoma with regression and their possible function as
prognostic predictors. Oncol Lett 2016;11:3354-60.

Published

15-09-2019

How to Cite

MUSTAFA, S. H., MUHAMAD, M., & AB-RAHIM, S. (2019). ABERRANT N-GLYCOSYLATION REGULATES INVASION OF MG-63 CELLS THROUGH EXTRACELLULAR MATRIX REMODELING. International Journal of Applied Pharmaceutics, 11(5), 75–79. https://doi.org/10.22159/ijap.2019.v11s5.T0053

Issue

Section

Original Article(s)