Heparanase is involved in the proliferation and invasion of nasopharyngeal carcinoma cells

Chen,Jinzhang; Zheng,Dayong; Shen,Jie; Ruan,Jian; Li,Aimin; Li,Wenmin; Xie,Guozhu; Luo,Xiaojun; Zhao,Peng; Zheng,Hang

doi:10.3892/or.2013.2325

Heparanase is involved in the proliferation and invasion of nasopharyngeal carcinoma cells

Authors:
- Jinzhang Chen
- Dayong Zheng
- Jie Shen
- Jian Ruan
- Aimin Li
- Wenmin Li
- Guozhu Xie
- Xiaojun Luo
- Peng Zhao
- Hang Zheng
View Affiliations

Affiliations: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Cell Biology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
Published online on: March 5, 2013 https://doi.org/10.3892/or.2013.2325
Pages: 1888-1894

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Heparanase (HPSE), an endo-β-D-glucuronidase, is overexpressed in nasopharyngeal carcinoma (NPC). The purpose of our study was to investigate the possible role of HPSE in the development of NPC. RNA interference (RNAi) using an HPSE small hairpin RNA (HPSE shRNA) was used to identify the effects of HPSE on the regulation of the malignant behaviors of NPC. CNE-2, a highly metastatic human NPC cell line in which HPSE mRNA and protein levels were detected to be the highest in three NPC cell lines involved in the research, was selected as a cell model in vitro and in vivo. The results showed that downregulation of HPSE significantly inhibited the proliferative and invasive abilities of CNE-2 cells partially through MAPK signaling. Compared with the parental NPC cells, HPSE-silenced cells exhibited attenuated capacity for developing tumors in nude mice, while the growth of tumor xenografts derived from these cells was dramatically suppressed. In conclusion, our results suggest that HPSE contributes to the proliferation and metastasis of NPC, and HPSE may be a potent molecular target for NPC treatment.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar
2	Wei WI and Sham JS: Nasopharyngeal carcinoma. Lancet. 365:2041–2054. 2005. View Article : Google Scholar : PubMed/NCBI
3	Sanderson RD, Yang Y, Suva LJ and Kelly T: Heparan sulfate proteoglycans and heparanase - partners in osteolytic tumor growth and metastasis. Matrix Biol. 23:341–352. 2004. View Article : Google Scholar : PubMed/NCBI
4	Simizu S, Ishida K and Osada H: Heparanase as a molecular target of cancer chemotherapy. Cancer Sci. 95:553–558. 2004. View Article : Google Scholar : PubMed/NCBI
5	Edovitsky E, Elkin M, Zcharia E, Peretz T and Vlodavsky I: Heparanase gene silencing, tumor invasiveness, angiogenesis, and metastasis. J Natl Cancer Inst. 96:1219–1230. 2004. View Article : Google Scholar : PubMed/NCBI
6	Zheng L, Jiang G, Mei H, et al: Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells. BMC Cancer. 10:332010. View Article : Google Scholar : PubMed/NCBI
7	Lerner I, Baraz L, Pikarsky E, et al: Function of heparanase in prostate tumorigenesis: potential for therapy. Clin Cancer Res. 14:668–676. 2008. View Article : Google Scholar : PubMed/NCBI
8	Bar-Sela G, Kaplan-Cohen V, Ilan N, Vlodavsky I and Ben-Izhak O: Heparanase expression in nasopharyngeal carcinoma inversely correlates with patient survival. Histopathology. 49:188–193. 2006. View Article : Google Scholar : PubMed/NCBI
9	Ogren S and Lindahl U: Cleavage of macromolecular heparin by an enzyme from mouse mastocytoma. J Biol Chem. 250:2690–2697. 1975.PubMed/NCBI
10	Nakajima M, Irimura T, Di Ferrante D, Di Ferrante N and Nicolson GL: Heparan sulfate degradation: relation to tumor invasive and metastatic properties of mouse B16 melanoma sublines. Science. 220:611–613. 1983. View Article : Google Scholar : PubMed/NCBI
11	Vlodavsky I, Fuks Z, Bar-Ner M, Ariav Y and Schirrmacher V: Lymphoma cell-mediated degradation of sulfated proteoglycans in the subendothelial extracellular matrix: relationship to tumor cell metastasis. Cancer Res. 43:2704–2711. 1983.PubMed/NCBI
12	Ilan N, Elkin M and Vlodavsky I: Regulation, function and clinical significance of heparanase in cancer metastasis and angiogenesis. Int J Biochem Cell Biol. 38:2018–2039. 2006. View Article : Google Scholar : PubMed/NCBI
13	Vreys V and David G: Mammalian heparanase: what is the message? J Cell Mol Med. 11:427–452. 2007. View Article : Google Scholar : PubMed/NCBI
14	Zhao W, Wang XS, Niu HT, Wang LL, Han BM and Xia SJ: Clinical relevance of heparanase mRNA expression in bladder cancer and its usefulness as a detection marker in voided urine. Mol Med Rep. 2:327–331. 2009.PubMed/NCBI
15	Nobuhisa T, Naomoto Y, Ohkawa T, et al: Heparanase expression correlates with malignant potential in human colon cancer. J Cancer Res Clin Oncol. 131:229–237. 2005. View Article : Google Scholar : PubMed/NCBI
16	Chen JQ, Zhan WH, He YL, et al: Relationship between heparanase mRNA expression in human gastric cancer and its clinicopathological features. Zhonghua Zhong Liu Za Zhi. 26:609–611. 2004.(In Chinese).
17	Theodoro TR, de Matos LL, Sant AA, et al: Heparanase expression in circulating lymphocytes of breast cancer patients depends on the presence of the primary tumor and/or systemic metastasis. Neoplasia. 9:504–510. 2007. View Article : Google Scholar
18	Leiser Y, Abu-El-Naaj I, Sabo E, et al: Prognostic value of heparanase expression and cellular localization in oral cancer. Head Neck. 33:871–877. 2011. View Article : Google Scholar : PubMed/NCBI
19	Brun R, Naroditsky I, Waterman M, et al: Heparanase expression by Barrett’s epithelium and during esophageal carcinoma progression. Mod Pathol. 22:1548–1554. 2009.
20	Quiros RM, Rao G, Plate J, et al: Elevated serum heparanase-1 levels in patients with pancreatic carcinoma are associated with poor survival. Cancer. 106:532–540. 2006. View Article : Google Scholar : PubMed/NCBI
21	Hong X, Nelson KK, DeCarvalho AC and Kalkanis SN: Heparanase expression of glioma in human and animal models. J Neurosurg. 113:261–269. 2010. View Article : Google Scholar : PubMed/NCBI
22	Kelly T, Miao HQ, Yang Y, et al: High heparanase activity in multiple myeloma is associated with elevated microvessel density. Cancer Res. 63:8749–8756. 2003.PubMed/NCBI
23	Bitan M, Polliack A, Zecchina G, et al: Heparanase expression in human leukemias is restricted to acute myeloid leukemias. Exp Hematol. 30:34–41. 2002. View Article : Google Scholar : PubMed/NCBI
24	Nakajima M, DeChavigny A, Johnson CE, Hamada J, Stein CA and Nicolson GL: Suramin. A potent inhibitor of melanoma heparanase and invasion. J Biol Chem. 266:9661–9666. 1991.PubMed/NCBI
25	Miao HQ, Liu H, Navarro E, Kussie P and Zhu Z: Development of heparanase inhibitors for anti-cancer therapy. Curr Med Chem. 13:2101–2111. 2006. View Article : Google Scholar : PubMed/NCBI
26	Miao HQ, Elkin M, Aingorn E, Ishai-Michaeli R, Stein CA and Vlodavsky I: Inhibition of heparanase activity and tumor metastasis by laminarin sulfate and synthetic phosphorothioate oligodeoxynucleotides. Int J Cancer. 83:424–431. 1999. View Article : Google Scholar : PubMed/NCBI
27	Karoli T, Liu L, Fairweather JK, et al: Synthesis, biological activity, and preliminary pharmacokinetic evaluation of analogues of a phosphosulfomannan angiogenesis inhibitor (PI-88). J Med Chem. 48:8229–8236. 2005. View Article : Google Scholar
28	Fjose A, Ellingsen S, Wargelius A and Seo HC: RNA interference: mechanisms and applications. Biotechnol Annu Rev. 7:31–57. 2001. View Article : Google Scholar
29	Zhang ZH, Chen Y, Zhao HJ, Xie CY, Ding J and Hou YT: Silencing of heparanase by siRNA inhibits tumor metastasis and angiogenesis of human breast cancer in vitro and in vivo. Cancer Biol Ther. 6:587–595. 2007. View Article : Google Scholar : PubMed/NCBI
30	Zhang Y, Li L, Wang Y, et al: Downregulating the expression of heparanase inhibits the invasion, angiogenesis and metastasis of human hepatocellular carcinoma. Biochem Biophys Res Commun. 358:124–129. 2007. View Article : Google Scholar : PubMed/NCBI
31	Jiang G, Zheng L, Pu J, et al: Small RNAs targeting transcription start site induce heparanase silencing through interference with transcription initiation in human cancer cells. PLoS One. 7:e313792012. View Article : Google Scholar
32	De Luca A, Maiello MR, D’Alessio A, Pergameno M and Normanno N: The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets. 16(Suppl 2): S17–S27. 2012.PubMed/NCBI