image: Figure 6: Administration of anti-V-ATPase nanobody does not affect intensity of leg metastases in mice receiving implanted 4T1-12B cells. 20 BALB/c mice were implanted with 4T1-12B cells in the mammary fat pad and then received injections of 66 μg of nanobody in PBS (or PBS alone for control mice) IP three times per week for 3 weeks. Prior to sacrifice mice were injected IP with luciferin and hind legs were removed and imaged ex vivo using a Perkin Elmer IVIS SpectrumCT In Vivo Imaging System. The intensity of the luminescence signal was quantitated using the Living Image® software.
Credit: 2024 Li et al.
“In the present study we describe the development of an inhibitory nanobody directed against an extracellular epitope present in the native V-ATPase c subunit.”
BUFFALO, NY- August 15, 2024 – A new research paper was published in Oncotarget's Volume 15 on August 14, 2024, entitled, “A nanobody against the V-ATPase c subunit inhibits metastasis of 4T1-12B breast tumor cells to lung in mice.”
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.
Researchers Zhen Li, Mohammed A. Alshagawi, Rebecca A. Oot, Mariam K. Alamoudi, Kevin Su, Wenhui Li, Michael P. Collins, Stephan Wilkens, and Michael Forgac from Tufts University School of Medicine; Tufts University; Dana Farber Cancer Institute, Harvard Medical School; University of Minnesota School of Medicine; Prince Sattam Bin Abdulaziz University; Korro Bio; SUNY Upstate Medical University; and Foghorn Therapeutics, have previously shown that selective inhibition of plasma membrane V-ATPases in breast tumor cells inhibits the invasion of these cells in vitro. They 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.”
The research team further found that injecting this nanobody into mice implanted with 4T1-12B cells orthotopically in the mammary fat pad inhibited the metastasis of tumor cells to the lungs.
“In conclusion, our results indicate that a nanobody directed against an extracellular epitope expressed on the surface of the V-ATPase is able to inhibit activity of cell surface V-ATPases in 4T1-12B breast cancer cells, inhibit in vitro invasion of these cells and inhibit metastasis of these cells to lung following their implantation in the mammary fat pad of mice.”
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28638
Correspondence to: Michael Forgac - michael.forgac@tufts.edu
Keywords: vacuolar ATPase; breast cancer; invasion; tumor metastasis; tumor growth
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Journal
Oncotarget
Method of Research
News article
Subject of Research
Animals
Article Title
A nanobody against the V-ATPase c subunit inhibits metastasis of 4T1-12B breast tumor cells to lung in mice
Article Publication Date
14-Aug-2024
COI Statement
Authors have no conflicts of interest to declare.