مورد إلكتروني
Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion
| العنوان: | Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion |
|---|---|
| المؤلفون: | Duivenvoorden, HM, Rautela, J, Edgington-Mitchell, LE, Spurling, A, Greening, DW, Nowell, CJ, Molloy, TJ, Robbins, E, Brockwell, NK, Lee-, CS, Chen, M, Holliday, A, Selinger, CI, Hu, M, Britt, KL, Stroud, DA, Bogyo, M, Moeller, A, Polyak, K, Sloane, BF, O'Toole, SA, Parker, BS |
| بيانات النشر: | WILEY 2017-12-01 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Mammography screening has increased the detection of early pre-invasive breast cancers, termed ductal carcinoma in situ (DCIS), increasing the urgency of identifying molecular regulators of invasion as prognostic markers to predict local relapse. Using the MMTV-PyMT breast cancer model and pharmacological protease inhibitors, we reveal that cysteine cathepsins have important roles in early-stage tumorigenesis. To characterize the cell-specific roles of cathepsins in early invasion, we developed a DCIS-like model, incorporating an immortalized myoepithelial cell line (N1ME) that restrained tumor cell invasion in 3D culture. Using this model, we identified an important myoepithelial-specific function of the cysteine cathepsin inhibitor stefin A in suppressing invasion, whereby targeted stefin A loss in N1ME cells blocked myoepithelial-induced suppression of breast cancer cell invasion. Enhanced invasion observed in 3D cultures with N1ME stefin A-low cells was reliant on cathepsin B activation, as addition of the small molecule inhibitor CA-074 rescued the DCIS-like non-invasive phenotype. Importantly, we confirmed that stefin A was indeed abundant in myoepithelial cells in breast tissue. Use of a 138-patient cohort confirmed that myoepithelial stefin A (cystatin A) is abundant in normal breast ducts and low-grade DCIS but reduced in high-grade DCIS, supporting myoepithelial stefin A as a candidate marker of lower risk of invasive relapse. We have therefore identified myoepithelial cell stefin A as a suppressor of early tumor invasion and a candidate marker to distinguish patients who are at low risk of developing invasive breast cancer, and can therefore be spared further treatment. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| مصطلحات الفهرس: | Journal Article |
| URL: | NHMRC/1047748 NHMRC/1127754 |
| الإتاحة: | Open access content. Open access content |
| أرقام أخرى: | UMV oai:jupiter.its.unimelb.edu.au:11343/198401 Duivenvoorden, H. M., Rautela, J., Edgington-Mitchell, L. E., Spurling, A., Greening, D. W., Nowell, C. J., Molloy, T. J., Robbins, E., Brockwell, N. K., Lee-, C. S., Chen, M., Holliday, A., Selinger, C. I., Hu, M., Britt, K. L., Stroud, D. A., Bogyo, M., Moeller, A., Polyak, K. ,... Parker, B. S. (2017). Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion. JOURNAL OF PATHOLOGY, 243 (4), pp.496-509. https://doi.org/10.1002/path.4990. 10.1002/path.4990 1096-9896 0022-3417 1315728004 |
| المصدر المساهم: | UNIV OF MELBOURNE From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1315728004 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |