Nanobody inhibits metastasis of breast tumor cells to lung in mice

A new research paper was published in Oncotarget titled, “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.

The researchers 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 researchers explained.

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,” the researchers said.

The research team includes 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.

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