Cancer cells metastasize far earlier than suspected

In In The News by Barbara Jacoby

By: Bradley J. Fikes


Solid tumors can metastasize far earlier than previously thought, according to a study by scientists at The Scripps Research Institute.

Tumor cells nearly always get into the bloodstream at the core, not the periphery, as the conventional model states. These cells become mobile before the primary tumor starts invading nearby tissue, the study found. So an apparently inactive tumor can in fact be seeding distant colonies.

These findings help explain how cancer can spread without giving any clues, said the open access study, published in Cell Reports. It can be found at The study was led by Elena I. Deryugina along with William B. Kiosses, both of TSRI.

If the study holds up under additional research, the traditional stages of cancer that place metastasis at an advanced stage of cancer will have to be scrapped. And doctors will need to factor in that uncertainty when pondering whether to watch an apparently low-threat tumor or aggressively treat it.

In addition, the study found a biomarker that predicts whether tumor cells will enter the bloodstream. This protein, EGFR, is already known to be involved in cancer. It appears to regulate formation of tumor blood vessels that are fully connected to the blood system.

Two human cancer lines, of fibrosarcoma and carcinoma, were tested in the ears of mice and chick embryos. Both of these structures provided visibility to watch the cancers take root and spread.

The human cancers were tagged with green fluorescent protein to allow their location to be tracked. Deryugina and Kiosses also mapped the 3D structure of the animal’s blood vessels.

With the fluorescent tagging and blood vessel mapping, the researchers were able to follow how the cancer cells entered the bloodstream. They found it took place in the tumor core. Fewer than 10 percent came from the cancer’s invasive edge.

To test the role of EGFR, the researchers silenced its expression in some of the tumors. The blood vessels in these tumors were substantially more disjointed and isolated, making it difficult for the tumor cells to enter.

“Furthermore, even if tumor cells had entered such compromised vasculature, those intravasated cells would likely remain physically trapped within the tumor core rather than carried away with blood flow,” the study stated.

Both the movement of tumor cells into the blood vessels and the connectivity of these vessels can be targeted with therapies, the study concluded. More research is ongoing to identify the molecular characteristics of tumor cells that allow them to do so, the study said.