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Article Open Access

Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D

  • Authors:
    • Chenfang Zhu
    • Xiaoliang Qi
    • Xin Zhou
    • Xin Nie
    • Yan Gu
  • View Affiliations / Copyright

    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
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3161-3171
    |
    Published online on: October 4, 2016
       https://doi.org/10.3892/or.2016.5143
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Abstract

In our previous studies, sulfatase 2 (Sulf2) was found to upregulate vascular endothelial growth factor-D (VEGF-D) expression in breast cancer. As VEGF-D plays an important role in lymphangiogenesis, we hypothesized that Sulf2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. To evaluate the functions of Sulf2 on lymphangiogenesis in breast cancer, proliferation, apoptosis, cell cycle, cell mobility and tube-formation of lymphatic endothelial cells (LECs) were measured in vitro. Lymphangiogenesis in nude mouse ears and breast cancer xenografts were examined in vivo. Furthermore, the expression levels of related signaling pathway genes were screened and verified in LECs. We found that Sulf2 significantly increased the mobility and tube formation of the LECs, inhibited cisplatin-induced LEC apoptosis, but had no effect on cell proliferation and the cell cycle. Moreover, recombinant Sulf2 (rSulf2) combined with VEGF-D further promoted the proliferation, cell cycle, mobility and tube-like structure formation in the LECs, and at the same time inhibited cisplatin-induced apoptosis especially in the late stage. Sulf2 also significantly increased the density of lymphatic vessels in mouse ears and breast cancer xenografts in vivo. AKT1 was also shown to be upregulated and activated by Sulf2. Our results confirmed that Sulf2 facilitated lymphangiogenesis in breast cancer cells by regulating VEGF-D and that the AKT1‑related signaling pathway was involved.
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1 

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

2 

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

3 

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

4 

Lamanna WC, Baldwin RJ, Padva M, Kalus I, Ten Dam G, van Kuppevelt TH, Gallagher JT, von Figura K, Dierks T and Merry CL: Heparan sulfate 6-O-endosulfatases: Discrete in vivo activities and functional co-operativity. Biochem J. 400:63–73. 2006. View Article : Google Scholar : PubMed/NCBI

5 

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

6 

Zhu C, He L, Zhou X, Nie X and Gu Y: Sulfatase 2 promotes breast cancer progression through regulating some tumor-related factors. Oncol Rep. 35:1318–1328. 2016.PubMed/NCBI

7 

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

8 

Al-Gayyar MM, Abbas A and Hamdan AM: Chemopreventive and hepatoprotective roles of adiponectin (SULF2 inhibitor) in hepatocelluar carcinoma. Biol Chem. 397:257–267. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Gill RM, Michael A, Westley L, Kocher HM, Murphy JI and Dhoot GK: SULF1/SULF2 splice variants differentially regulate pancreatic tumour growth progression. Exp Cell Res. 324:157–171. 2014. View Article : Google Scholar : PubMed/NCBI

10 

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

11 

Lui NS, Yang YW, van Zante A, Buchanan P, Jablons DM and Lemjabbar-Alaoui H: SULF2 expression is a potential diagnostic and prognostic marker in lung cancer. PLoS One. 11:e01489112016. View Article : Google Scholar : PubMed/NCBI

12 

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 : PubMed/NCBI

13 

Plate K: From angiogenesis to lymphangiogenesis. Nat Med. 7:151–152. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Karkkainen MJ and Petrova TV: Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene. 19:5598–5605. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Sleeman JP and Thiele W: Tumor metastasis and the lymphatic vasculature. Int J Cancer. 125:2747–2756. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Reis-Filho JS and Schmitt FC: Lymphangiogenesis in tumors: What do we know? Microsc Res Tech. 60:171–180. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Tammela T, Petrova TV and Alitalo K: Molecular lymphangiogenesis: New players. Trends Cell Biol. 15:434–441. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Acs G, Paragh G, Rakosy Z, Laronga C and Zhang PJ: The extent of retraction clefts correlates with lymphatic vessel density and VEGF-C expression and predicts nodal metastasis and poor prognosis in early-stage breast carcinoma. Mod Pathol. 25:163–177. 2012.PubMed/NCBI

19 

Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K and Detmar M: Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 7:192–198. 2001. View Article : Google Scholar : PubMed/NCBI

20 

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

21 

Joy AA, Ghosh M, Fernandes R and Clemons MJ: Systemic treatment approaches in Ηer2-negative advanced breast cancer-guidance on the guidelines. Curr Oncol. 22:(Suppl 1). S29–S42. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Fina E, Callari M, Reduzzi C, DAiuto 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 : PubMed/NCBI

23 

Takei H, Kurosumi M, Yoshida T, Ninomiya J, Hagiwara Y, Kamimura M, Hayashi Y, Tozuka K, Suemasu K, Inoue K, et al: Current trends of sentinel lymph node biopsy for breast cancer - a surgeons perspective. Breast Cancer. 14:362–370. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Karpanen T, Wirzenius M, Mäkinen T, Veikkola T, Haisma HJ, Achen MG, Stacker SA, Pytowski B, Ylä-Herttuala S and Alitalo K: Lymphangiogenic growth factor responsiveness is modulated by postnatal lymphatic vessel maturation. Am J Pathol. 169:708–718. 2006. View Article : Google Scholar : PubMed/NCBI

25 

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

26 

Cherng JM, Lin CM, Lin CL, Huang SM, Chang HL, Lee CC, Chiang LC and Chang PY: Effects of VEGF121 and/or VEGF165 gene transfection on collateral circulation development. J Formos Med Assoc. 99:603–611. 2000.PubMed/NCBI

27 

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

28 

Okamoto K, Oshika Y, Fukushima Y, Ohnishi Y, Tokunaga T, Tomii Y, Kijima H, Yamazaki H, Ueyama Y, Tamaoki N, et al: Xenografts of human solid tumors frequently express cellular-associated isoform of vascular endothelial growth factor (VEGF) 189. Oncol Rep. 6:1201–1204. 1999.PubMed/NCBI

29 

Karnezis T, Shayan R, Caesar C, Roufail S, Harris NC, Ardipradja K, Zhang YF, Williams SP, Farnsworth RH, Chai MG, et al: VEGF-D promotes tumor metastasis by regulating prostaglandins produced by the collecting lymphatic endothelium. Cancer Cell. 21:181–195. 2012. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhu C, Qi X, Zhou X, Nie X and Gu Y: Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. Oncol Rep 36: 3161-3171, 2016.
APA
Zhu, C., Qi, X., Zhou, X., Nie, X., & Gu, Y. (2016). Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. Oncology Reports, 36, 3161-3171. https://doi.org/10.3892/or.2016.5143
MLA
Zhu, C., Qi, X., Zhou, X., Nie, X., Gu, Y."Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D". Oncology Reports 36.6 (2016): 3161-3171.
Chicago
Zhu, C., Qi, X., Zhou, X., Nie, X., Gu, Y."Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D". Oncology Reports 36, no. 6 (2016): 3161-3171. https://doi.org/10.3892/or.2016.5143
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu C, Qi X, Zhou X, Nie X and Gu Y: Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. Oncol Rep 36: 3161-3171, 2016.
APA
Zhu, C., Qi, X., Zhou, X., Nie, X., & Gu, Y. (2016). Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D. Oncology Reports, 36, 3161-3171. https://doi.org/10.3892/or.2016.5143
MLA
Zhu, C., Qi, X., Zhou, X., Nie, X., Gu, Y."Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D". Oncology Reports 36.6 (2016): 3161-3171.
Chicago
Zhu, C., Qi, X., Zhou, X., Nie, X., Gu, Y."Sulfatase 2 facilitates lymphangiogenesis in breast cancer by regulating VEGF-D". Oncology Reports 36, no. 6 (2016): 3161-3171. https://doi.org/10.3892/or.2016.5143
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