Matrix detachment and proteasomal inhibitors diminish Sulf-2 expression in breast cancer cell lines and mouse xenografts
| العنوان: | Matrix detachment and proteasomal inhibitors diminish Sulf-2 expression in breast cancer cell lines and mouse xenografts |
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| المؤلفون: | Laura Lorenzon, Viji Shridhar, Robert Busby, M Villa, Julian R. Molina, Sung-Hoon Kim, Ashwani Khurana, Deok Jung-Beom, Xiaoping He, Alfonso Baldi, Matthew P. Goetz |
| المساهمون: | Khurana, A, Jung Beom, D, He, X, Kim, Sh, Busby, Rc, Lorenzon, L, Villa, M, Baldi, Alfonso, Molina, J, Goetz, Mp, Shridhar, V. |
| المصدر: | Clinical & Experimental Metastasis. 30:407-415 |
| بيانات النشر: | Springer Science and Business Media LLC, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Cancer Research, Programmed cell death, Blotting, Western, Cell, Lactacystin, Apoptosis, Breast Neoplasms, Biology, Real-Time Polymerase Chain Reaction, Article, Immunoenzyme Techniques, Mice, chemistry.chemical_compound, Breast cancer, Tumor Cells, Cultured, medicine, Animals, Humans, RNA, Messenger, RNA, Small Interfering, Cell Proliferation, Reverse Transcriptase Polymerase Chain Reaction, Cell growth, Bortezomib, Carcinoma, Ductal, Breast, Growth factor, General Medicine, Ductal carcinoma, medicine.disease, Xenograft Model Antitumor Assays, Molecular biology, Extracellular Matrix, Settore MED/18 - Chirurgia Generale, Carcinoma, Lobular, medicine.anatomical_structure, Sulfatase 2, Oncology, chemistry, Female, Neoplasm Grading, Sulfatases, Sulfotransferases, Proteasome Inhibitors, medicine.drug |
| الوصف: | 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. © 2013 Springer Science+Business Media Dordrecht. |
| تدمد: | 1573-7276 0262-0898 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eda244d9cf06b1dfde85c32d1c23e8e1Test https://doi.org/10.1007/s10585-012-9546-5Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....eda244d9cf06b1dfde85c32d1c23e8e1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15737276 02620898 |
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