Journal article

Myoepithelial cell-specific expression of stefin A as a suppressor of early breast cancer invasion

HM Duivenvoorden, J Rautela, LE Edgington-Mitchell, A Spurling, DW Greening, CJ Nowell, TJ Molloy, E Robbins, NK Brockwell, CS Lee, M Chen, A Holliday, CI Selinger, M Hu, KL Britt, DA Stroud, M Bogyo, A Möller, K Polyak, BF Sloane Show all

Journal of Pathology | WILEY | Published : 2017

Abstract

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 f..

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Grants

Awarded by Appalachian Regional Commission


Funding Acknowledgements

We gratefully thank Peter Lock of the LIMS Microscopy and Imaging Facility, the staff at La Trobe University Central Animal House for technical assistance, and the La Trobe Comprehensive Proteomics Platform for access to equipment and expertise employed in this study. We express our gratitude to Dr Elgene Lim for the gift of the CAL120 cell line. We also thank Dr Kaylene Simpson and Dr Iva Nikolic from the Peter MacCallum Cancer Centre for their assistance with siRNA. This work was supported by grant funding from the National Health and Medical Research Council (NHMRC) (BSP 1047748 and 1127754); fellowship support to BSP from the ARC (FT130100671), DAS from the NHMRC (1070916), and SOT from the NBCF (Practitioner Fellowship PRAC-16-006); and scholarship support from the Cancer Council Victoria (to HMD). Support from the Sydney Breast Cancer Foundation is also gratefully acknowledged.