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 Shridhar

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)407-415
Number of pages9
JournalClinical and Experimental Metastasis
Volume30
Issue number4
DOIs
StatePublished - Apr 1 2013

Keywords

  • Breast cancer
  • Growth factor
  • Sulfatase 2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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