Sulfatase 2 promotes breast cancer progression through regulating some tumor-related factors

Zhu,Chenfang; He,Liu; Zhou,Xin; Nie,Xin; Gu,Yan

doi:10.3892/or.2015.4525

Sulfatase 2 promotes breast cancer progression through regulating some tumor-related factors

Authors:
- Chenfang Zhu
- Liu He
- Xin Zhou
- Xin Nie
- Yan Gu
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Affiliations: Department of General Surgery, Shanghai Ninth People's Hospital Affiliated with Shanghai Jiaotong University, School of Medicine, Shanghai 200011, P.R. China, Department of Surgery, George Washington University, Washington, DC 20052, USA
Published online on: December 28, 2015 https://doi.org/10.3892/or.2015.4525
Pages: 1318-1328
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In previous studies Sulf2 has been evidenced to play an important role in tumor progression through editing sulfate moieties on heparan sulfate proteoglycans (HSPGs) and modulating heparin binding growth factors. However, the role of Sulf2 in breast cancer progression is still poorly understood. In the present study, we hypothesized that Sulf2 promoted breast cancer progression. Two different breast cancer cell lines, MCF-7 and MDA-MB-231, were chosen for this study because of high and low Sulf2 expression levels. We also altered their Sulf2 expression by establishing Sulf2 knockdown and overexpressing breast cancer cell lines MCF-7 shSulf2 and MDA-MB-231 Sulf2. To evaluate the functions of Sulf2, cell proliferation, apoptosis, cell cycle, invasion, mobility and adhesion of these cell lines were measured in vitro, and xenograft formation, invasion and metastasis ability were examined in vivo. Furthermore, expression of related genes were screened and were certified in these cell lines. We found that Sulf2 increased breast cancer proliferation, invasion, mobility and adhesion both in vitro and in vivo. Sulf2 also decreased cisplatin inducing breast cancer apoptosis without affecting the cell cycle. Sulf2 upregulated c-fos induced growth factor (FIGF) and nuclear receptor subfamily 4 group A member 3 (NR4A3) expression and downregulated the cluster of differentiation 82 (CD82) and platelet-derived growth factor C (PDGFC) expression in breast cancer. Our data confirmed that Sulf2 promoted breast cancer progression and regulated the expression of tumor-related genes in breast cancer.

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1	Joy AA, Ghosh M, Fernandes R and Clemons MJ: Systemic treatment approaches in her2-negative advanced breast cancer-guidance on the guidelines. Curr Oncol. 22(Suppl 1): S29–S42. 2015. View Article : Google Scholar : PubMed/NCBI
2	Fina E, Callari M, Reduzzi C, D'Aiuto F, Mariani G, Generali D, Pierotti MA, Daidone MG and Cappelletti V: Gene expression profiling of circulating tumor cells in breast cancer. Clin Chem. 61:278–289. 2015. View Article : Google Scholar
3	Bishop JR, Schuksz M and Esko JD: Heparan sulphate proteoglycans fine-tune mammalian physiology. Nature. 446:1030–1037. 2007. View Article : Google Scholar : PubMed/NCBI
4	Turnbull J, Powell A and Guimond S: Heparan sulfate: Decoding a dynamic multifunctional cell regulator. Trends Cell Biol. 11:75–82. 2001. View Article : Google Scholar : PubMed/NCBI
5	Rosen SD and Lemjabbar-Alaoui H: Sulf-2: An extracellular modulator of cell signaling and a cancer target candidate. Expert Opin Ther Targets. 14:935–949. 2010. View Article : Google Scholar : PubMed/NCBI
6	Maltseva I, Chan M, Kalus I, Dierks T and Rosen SD: The SULFs, extracellular sulfatases for heparan sulfate, promote the migration of corneal epithelial cells during wound repair. PLoS One. 8:e696422013. View Article : Google Scholar : PubMed/NCBI
7	Fujita K, Takechi E, Sakamoto N, Sumiyoshi N, Izumi S, Miyamoto T, Matsuura S, Tsurugaya T, Akasaka K and Yamamoto T: HpSulf, a heparan sulfate 6-O-endosulfatase, is involved in the regulation of VEGF signaling during sea urchin development. Mech Dev. 127:235–245. 2010. View Article : Google Scholar
8	Uchimura K, Morimoto-Tomita M, Bistrup A, Li J, Lyon M, Gallagher J, Werb Z and Rosen SD: HSulf-2, an extracellular endoglucosamine-6-sulfatase, selectively mobilizes heparin-bound growth factors and chemokines: Effects on VEGF, FGF-1, and SDF-1. BMC Biochem. 7:22006. View Article : Google Scholar : PubMed/NCBI
9	Khurana A, Jung-Beom D, He X, Kim SH, Busby RC, Lorenzon L, Villa M, Baldi A, Molina J, Goetz MP, et al: Matrix detachment and proteasomal inhibitors diminish Sulf2 expression in breast cancer cell lines and mouse xenografts. Clin Exp Metastasis. 30:407–415. 2013. View Article : Google Scholar : PubMed/NCBI
10	Hammond E, Khurana A, Shridhar V and Dredge K: The role of heparanase and sulfatases in the modification of heparan sulfate proteoglycans within the tumor microenvironment and opportunities for novel cancer therapeutics. Front Oncol. 4:1952014. View Article : Google Scholar : PubMed/NCBI
11	Khurana A, Liu P, Mellone P, Lorenzon L, Vincenzi B, Datta K, Yang B, Linhardt RJ, Lingle W, Chien J, et al: HSulf-1 modulates FGF2- and hypoxia-mediated migration and invasion of breast cancer cells. Cancer Res. 71:2152–2161. 2011. View Article : Google Scholar : PubMed/NCBI
12	Peterson SM, Iskenderian A, Cook L, Romashko A, Tobin K, Jones M, Norton A, Gómez-Yafal A, Heartlein MW, Concino MF, et al: Human sulfatase 2 inhibits in vivo tumor growth of MDA-MB-231 human breast cancer xenografts. BMC Cancer. 10:4272010. View Article : Google Scholar : PubMed/NCBI
13	Lai JP, Sandhu DS, Yu C, Han T, Moser CD, Jackson KK, Guerrero RB, Aderca I, Isomoto H, Garrity-Park MM, et al: Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma. Hepatology. 47:1211–1222. 2008. View Article : Google Scholar : PubMed/NCBI
14	Nawroth R, van Zante A, Cervantes S, McManus M, Hebrok M and Rosen SD: Extracellular sulfatases, elements of the Wnt signaling pathway, positively regulate growth and tumorigenicity of human pancreatic cancer cells. PLoS. 2:e3922007. View Article : Google Scholar
15	Morimoto-Tomita M, Uchimura K, Bistrup A, Lum DH, Egeblad M, Boudreau N, Werb Z and Rosen SD: Sulf-2, a proangiogenic heparan sulfate endosulfatase, is upregulated in breast cancer. Neoplasia. 7:1001–1010. 2005. View Article : Google Scholar : PubMed/NCBI
16	Lemjabbar-Alaoui H, van Zante A, Singer MS, Xue Q, Wang YQ, Tsay D, He B, Jablons DM and Rosen SD: Sulf-2, a heparan sulfate endosulfatase, promotes human lung carcinogenesis. Oncogene. 29:635–646. 2010. View Article : Google Scholar :
17	Rosen SD and Lemjabbar-Alaoui H: Sulf-2: An extracellular modulator of cell signaling and a cancer target candidate. Expert Opin Ther Targets. 14:935–949. 2010. View Article : Google Scholar : PubMed/NCBI
18	Zhu C, Qi X, Chen Y, Sun B, Dai Y and Gu Y: PI3K/Akt and MAPK/ERK1/2 signaling pathways are involved in IGF-1-induced VEGF-C upregulation in breast cancer. J Cancer Res Clin Oncol. 137:1587–1594. 2011. View Article : Google Scholar : PubMed/NCBI
19	Khurana A, Beleford D, He X, Chien J and Shridhar V: Role of heparan sulfatases in ovarian and breast cancer. Am J Cancer Res. 3:34–45. 2013.PubMed/NCBI
20	Khurana A, McKean H, Kim H, Kim SH, McGuire J, Roberts LR, Goetz MP and Shridhar V: Silencing of HSulf-2 expression in http://MCF10DCIS.comurisimpleMCF10DCIS.com cells attenuate ductal carcinoma in situ progression to invasive ductal carcinoma in vivo. Breast Cancer Res. 14:R432012. View Article : Google Scholar
21	Guo J, Huang Y, Yang L, Xie Z, Song S, Yin J, Kuang L and Qin W: Association between abortion and breast cancer: An updated systematic review and meta-analysis based on prospective studies. Cancer Causes Control. 26:811–819. 2015. View Article : Google Scholar : PubMed/NCBI
22	Scully OJ, Bay BH, Yip G and Yu Y: Breast cancer metastasis. Cancer Genomics Proteomics. 9:311–320. 2012.PubMed/NCBI
23	Sun DW, Zhang YY, Qi Y, Zhou XT and Lv GY: Prognostic significance of MMP-7 expression in colorectal cancer: A meta-analysis. Cancer Epidemiol. 39:135–142. 2015. View Article : Google Scholar : PubMed/NCBI
24	Kasthuri RS, Taubman MB and Mackman N: Role of tissue factor in cancer. J Clin Oncol. 27:4834–4838. 2009. View Article : Google Scholar : PubMed/NCBI
25	Eichhorn ME, Kleespies A, Angele MK, Jauch KW and Bruns CJ: Angiogenesis in cancer: Molecular mechanisms, clinical impact. Langenbecks Arch Surg. 392:371–379. 2007. View Article : Google Scholar : PubMed/NCBI
26	Harris NC, Davydova N, Roufail S, Paquet-Fifield S, Paavonen K, Karnezis T, Zhang YF, Sato T, Rothacker J, Nice EC, et al: The propeptides of VEGF-D determine heparin binding, receptor heterodimerization, and effects on tumor biology. J Biol Chem. 288:8176–8186. 2013. View Article : Google Scholar : PubMed/NCBI
27	Gu Y, Qi X and Guo S: Lymphangiogenesis induced by VEGF-C and VEGF-D promotes metastasis and a poor outcome in breast carcinoma: A retrospective study of 61 cases. Clin Exp Metastasis. 25:717–725. 2008. View Article : Google Scholar : PubMed/NCBI