Research Papers:
A nanobody against the V-ATPase c subunit inhibits metastasis of 4T1-12B breast tumor cells to lung in mice
PDF | Full Text | How to cite | Press Release
Metrics: PDF 391 views | Full Text 1267 views | ?
Abstract
Zhen Li2,4,*, Mohammed A. Alshagawi2,5,*, Rebecca A. Oot8, Mariam K. Alamoudi1,6, Kevin Su2,7, Wenhui Li2, Michael P. Collins3,9, Stephan Wilkens8 and Michael Forgac1,2,3
1 Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111, USA
2 Program in Pharmacology and Drug Development, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA
3 Program in Cellular, Molecular and Developmental Biology, Graduate School of Biomedical Sciences, Tufts University, Boston, MA 02111, USA
4 Department of Cancer Immunology and Virology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA
5 Department of Pharmacology, University of Minnesota School of Medicine, MN 55455, USA
6 Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
7 Korro Bio, Cambridge, MA 02139, USA
8 Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
9 Foghorn Therapeutics, Cambridge, MA 02139, USA
* These authors contributed equally to this work
Correspondence to:
Michael Forgac, | email: | [email protected] |
Keywords: vacuolar ATPase; breast cancer; invasion; tumor metastasis; tumor growth
Received: June 28, 2024 Accepted: July 30, 2024 Published: August 14, 2024
ABSTRACT
The vacuolar H+-ATPase (V-ATPase) is an ATP-dependent proton pump that functions to control the pH of intracellular compartments as well as to transport protons across the plasma membrane of various cell types, including cancer cells. We have previously shown that selective inhibition of plasma membrane V-ATPases in breast tumor cells inhibits the invasion of these cells in vitro. We have now developed a nanobody directed against an extracellular epitope of the mouse V-ATPase c subunit. We show that treatment of 4T1-12B mouse breast cancer cells with this nanobody inhibits V-ATPase-dependent acidification of the media and invasion of these cells in vitro. We further find that injection of this nanobody into mice implanted with 4T1-12B cells orthotopically in the mammary fat pad inhibits metastasis of tumor cells to lung. These results suggest that plasma membrane V-ATPases represent a novel therapeutic target to limit breast cancer metastasis.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 28638