Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

Online
ISSN
1437-4315
See all formats and pricing
More options …
Volume 393, Issue 12 (Dec 2012)

Issues

Three-dimensional cultures modeling premalignant progression of human breast epithelial cells: role of cysteine cathepsins

Stefanie R. Mullins
  • Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
  • Present Address: MedImmune, Cambridge, UK
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mansoureh Sameni / Galia Blum
  • Departments of Microbiology & Immunology and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Present Address: School of Pharmacy, Institute for Drug Research, Hebrew University of Jerusalem, Jerusalem, Israel
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Matthew Bogyo
  • Departments of Microbiology & Immunology and Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Bonnie F. Sloane
  • Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
  • Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Kamiar Moin
  • Corresponding author
  • Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
  • Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2012-11-13 | DOI: https://doi.org/10.1515/hsz-2012-0252

Abstract

The expression of the cysteine protease cathepsin B is increased in early stages of human breast cancer. To assess the potential role of cathepsin B in premalignant progression of breast epithelial cells, we employed a 3D reconstituted basement membrane overlay culture model of MCF10A human breast epithelial cells and isogenic variants that replicate the in vivo phenotypes of hyperplasia (MCF10AneoT) and atypical hyperplasia (MCF10AT1). MCF10A cells developed into polarized acinar structures with central lumens. In contrast, MCF10AneoT and MCF10AT1 cells form larger structures in which the lumens are filled with cells. CA074Me, a cell-permeable inhibitor selective for the cysteine cathepsins B and L, reduced proliferation and increased apoptosis of MCF10A, MCF10AneoT and MCF10AT1 cells in 3D culture. We detected active cysteine cathepsins in the isogenic MCF10 variants in 3D culture with GB111, a cell-permeable activity-based probe, and established differential inhibition of cathepsin B in our 3D cultures. We conclude that cathepsin B promotes proliferation and premalignant progression of breast epithelial cells. These findings are consistent with studies by others showing that deletion of cathepsin B in the transgenic MMTV-PyMT mice, a murine model that is predisposed to development of mammary cancer, reduces malignant progression.

This article offers supplementary material which is provided at the end of the article.

Keywords: activity-based probes; breast cancer; cysteine cathepsins; premalignant progression; protease inhibitors

About the article

Corresponding author: Kamiar Moin, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA; and Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA


Received: 2012-07-12

Accepted: 2012-10-04

Published Online: 2012-11-13

Published in Print: 2012-12-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2012-0252.

Export Citation

©2012 by Walter de Gruyter Berlin Boston. Copyright Clearance Center

Supplementary Article Materials

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
LUOSHENG ZHANG, LIXIA WEI, GUANZHU SHEN, BENFU HE, WEI GONG, NA MIN, LI ZHANG, YUXIN DUAN, JINGRAN XIE, HUIYAN LUO, and XINGWANG GAO
Molecular Medicine Reports, 2015, Volume 11, Number 1, Page 468
[2]
Sneha Balani, Long V. Nguyen, and Connie J. Eaves
Nature Communications, 2017, Volume 8, Page 15422
[3]
Mansoureh Sameni, Dora Cavallo-Medved, Omar E. Franco, Anita Chalasani, Kyungmin Ji, Neha Aggarwal, Arulselvi Anbalagan, Xuequn Chen, Raymond R. Mattingly, Simon W. Hayward, and Bonnie F. Sloane
Breast Cancer Research, 2017, Volume 19, Number 1
[4]
Sarah L Maguire, Barrie Peck, Patty T Wai, James Campbell, Holly Barker, Aditi Gulati, Frances Daley, Simon Vyse, Paul Huang, Christopher J Lord, Gillian Farnie, Keith Brennan, and Rachael Natrajan
The Journal of Pathology, 2016, Volume 240, Number 3, Page 315
[5]
Neha Aggarwal, Ann Marie Santiago, David Kessel, and Bonnie F. Sloane
Breast Cancer Research and Treatment, 2015, Volume 154, Number 2, Page 251
[6]
Eun Kyung Lee, Chan Woo Kim, Hiroyuki Kawanami, Akihiro Kishimura, Takuro Niidome, Takeshi Mori, and Yoshiki Katayama
RSC Adv., 2015, Volume 5, Number 104, Page 85816
[7]
Kyungmin Ji, Joshua Heyza, Dora Cavallo-Medved, and Bonnie F. Sloane
Biochimie, 2016, Volume 122, Page 68
[8]
Kingsley O. Osuala, Mansoureh Sameni, Seema Shah, Neha Aggarwal, Michelle L. Simonait, Omar E. Franco, Yan Hong, Simon W. Hayward, Fariba Behbod, Raymond R. Mattingly, and Bonnie F. Sloane
BMC Cancer, 2015, Volume 15, Number 1
[9]
Daniela Loessner, Boris Michael Holzapfel, and Judith Ann Clements
Advanced Drug Delivery Reviews, 2014, Volume 79-80, Page 193
[10]
Santhi Maniganda, Vandana Sankar, Jyothi B. Nair, K. G. Raghu, and Kaustabh K. Maiti
Org. Biomol. Chem., 2014, Volume 12, Number 34, Page 6564
[11]
Daniela Loessner, Simone C. Rizzi, Kathryn S. Stok, Tobias Fuehrmann, Brett Hollier, Viktor Magdolen, Dietmar W. Hutmacher, and Judith A. Clements
Biomaterials, 2013, Volume 34, Number 30, Page 7389

Comments (0)

Please log in or register to comment.
Log in