Clinical & Experimental Metastasis

, Volume 30, Issue 4, pp 407–415 | Cite as

Matrix detachment and proteasomal inhibitors diminish Sulf-2 expression in breast cancer cell lines and mouse xenografts

  • Ashwani Khurana
  • Deok Jung-Beom
  • Xiaoping He
  • Sung-Hoon Kim
  • Robert C. Busby
  • Laura Lorenzon
  • Massimo Villa
  • Alfonso Baldi
  • Julian Molina
  • Matthew P. Goetz
  • Viji ShridharEmail author
Research Paper


Sulfatase 2 (Sulf-2) has been previously shown to be upregulated in breast cancer. Sulf-2 removes sulfate moieties on heparan sulfate proteoglycans which in turn modulate heparin binding growth factor signaling. Here we report that matrix detachment resulted in decreased Sulf-2 expression in breast cancer cells and increased cleavage of poly ADP-ribose polymerase. Silencing of Sulf-2 promotes matrix detachment induced cell death in MCF10DCIS cells. In an attempt to identify Sulf-2 specific inhibitor, we found that proteasomal inhibitors such as MG132, Lactacystin and Bortezomib treatment abolished Sulf-2 expression in multiple breast cancer cell lines. Additionally, we show that Bortezomib treatment of MCF10DCIS cell xenografts in mouse mammary fat pads significantly reduced tumor size, caused massive apoptosis and more importantly reduced Sulf-2 levels in vivo. Finally, our immunohistochemistry analysis of Sulf-2 expression in cohort of patient derived breast tumors indicates that Sulf-2 is significantly upregulated in autologous metastatic lesions compared to primary tumors (p < 0.037, Pearson correlation, Chi-Square analysis). In all, our data suggest that Sulf-2 might play an important role in breast cancer progression from ductal carcinoma in situ into an invasive ductal carcinoma potentially by resisting cell death.


Sulfatase 2 Growth factor Breast cancer 



Sulfatase 2


Matrix metalloproteases


Fibroblast growth factor 2


Heparan sulfate proteoglycans



We thank members of Shridhar’s lab for insightful discussions. This work was supported by grants from the NCI, National Institutes of Health (CA106954-04), the Mayo Clinic (to VS) and the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST 2011-0006220).

Conflict of interest

Authors do not have any conflict of interest.

Supplementary material

10585_2012_9546_MOESM1_ESM.doc (122 kb)
Supplementary material 1 (DOC 122 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Ashwani Khurana
    • 1
  • Deok Jung-Beom
    • 2
  • Xiaoping He
    • 1
  • Sung-Hoon Kim
    • 2
  • Robert C. Busby
    • 1
  • Laura Lorenzon
    • 3
  • Massimo Villa
    • 4
  • Alfonso Baldi
    • 5
  • Julian Molina
    • 6
  • Matthew P. Goetz
    • 6
  • Viji Shridhar
    • 1
    Email author
  1. 1.Department of Experimental PathologyMayo Clinic College of MedicineRochesterUSA
  2. 2.College of Oriental Medicine, Kyung Hee UniversitySeoulSouth Korea
  3. 3.Department of Surgery “A”Second Faculty of Medicine, “La Sapienza” UniversityRomeItaly
  4. 4.Department of SurgeryUniversity Hospital of Tor VergataRomeItaly
  5. 5.Section of OncologyCampus BioMedico UniversityRomeItaly
  6. 6.Department of OncologyMayo Clinic College of MedicineRochesterUSA

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