Research News

Low Oxygen Environment in Tumors Create More Aggressive Cells

Using a new technology to capture and study tumor cells circulating the blood stream, researchers at Stanford University have demonstrated that the low oxygen environment inside tumors produces cells that are aggressively metastatic. Furthermore, the investigators pinpointed some of the proteins associated with this more aggressive state.

Reporting its work in the British Journal of Cancer, a team of investigators led by Stefanie Jeffrey used magnetic beads coated with an antibody known to bind to circulating tumor cells (CTCs) to capture these rare cells as they move through the blood stream.  This technique, which the researchers have named MagSweeper, is gentle enough that the researchers were able to grow the captured cells in culture for further study or to implant them into mice, where they developed tumors. In the current study, the investigators captured CTCs shed by so-called triple negative breast tumors, the most aggressive form of breast cancer and the one least responsive to therapy. These tumors have large regions in which oxygen levels are low (hypoxia) or almost zero (anoxia).

The investigators found that CTCs shed by these highly hypoxic and anoxic tumors produced large amounts of proteins expressed by cells growing in low oxygen environments even though the CTCs were captured in the oxygen-rich blood stream and grown in an oxygen-rich culture medium. In fact, the CTCs, compared to the cells from which the original tumors were derived, produced more of these proteins than expected.

When raised in culture, the CTCs grew more rapidly and produced bigger colonies than did the malignant cells used to seed the initial triple negative breast tumors. This finding carried over to the in vivo world, too – when implanted into mice, the CTCs created larger tumors that rapidly metastasized to the lungs. 

This work is detailed in a paper titled, “Circulating tumor cells demonstrated an altered response to hypoxia and an aggressive phenotype.” An abstract of this paper is available at the journal’s Web site.
View abstract