New Discovery about Oxygen and Cancer Cells
Scientists are drawing closer to understanding how cancer cells pursue oxygen, which they need to survive.
The discovery represents a step toward understanding one of the ways cancer spreads.
In a paper published in the Proceedings of the National Academy of Sciences, bioengineers from Johns Hopkins University and the University of Pennsylvania report results of their work showing how sarcoma cells in mice pursue a path toward greater concentrations of oxygen, almost as if they were following a widening trail of breadcrumbs. That path is suggested to lead the cells to blood vessels, through which the cells can spread to other parts of the body.
“If you think about therapeutic targets, you could target this process specifically,” said Sharon Gerecht, professor in Johns Hopkins University’s Whiting School of Engineering’s Department of Chemical and Biomolecular Engineering, and a lead author of the study. She acknowledged that clinical application is a long way off, but said these results reached after three years of study in her laboratory provide clues about a key part of the life cycle of soft-tissue sarcomas and also a proven way to test cancer treatments in the lab.
These microscope images show sarcoma cancer cells in a hydrogel migrating out of a tumor in greater numbers in the hypoxic, or low-oxygen environment at the bottom, than in the surroundings where the oxygen level is about the same as the atmosphere, or nonhypoxic, at the top. [Image courtesy of Daniel Lewis, Johns Hopkins University].
Sarcoma is a cancer that affects connective tissue, including bones, muscles, tendons, cartilage, nerves, fat and some blood vessels. The study focused specifically on soft tissue sarcoma that does not affect bones, which is diagnosed in some 13,000 patients a year in the United States. Roughly a quarter to half of those patients develop recurring and spreading, or metastasizing, cancer.
Cancers of all sorts are known to thrive with little oxygen, and researchers have looked at the role of low oxygen conditions in tumor development. Less well understood is how cancer cells respond to varying oxygen concentrations in their early stages. That was the focus of this research.
Gerecht and her seven co-authors – four affiliated with Hopkins, three with the University of Pennsylvania – tracked thousands of early-stage cancer cells taken from mice as they moved through a mockup of bodily tissue made of clear gel in a petri dish. The hydrogel – a water-based material with the consistency of gelatin — replicates the environment surrounding cancer cells in human tissue.
Kyung Min Park, a previous postdoctoral researcher in the Johns Hopkins lab, developed the hydrogel-cancer cell system and Daniel Lewis, a Johns Hopkins graduate student, analyzed cellular migration and responses to rising oxygen concentrations, or “gradients.”