February 27, 2004

Cancer cells can compress blood vessels, block entry of drugs

A growing tumor needs an increased blood supply for its proliferating cells. But these new vessels are often disorganized and abnormal and can actually block therapeutic agents from reaching malignant cells. In the Feb. 19 issue of Nature, MGH researchers describe how proliferating cancer cells compress both blood and lymphatic vessels within tumors.

"We've known for several years that internal pressure can make it difficult for many drugs to penetrate into a tumor," says Rakesh Jain, PhD, (left) director of the Steele Laboratory in the Department of Radiation Therapy. "Much of our work has focused on fluid pressure within tumors, but this was the first look at solid pressure."

Since fluid pressures inside both tumors and their blood vessels are almost equal, the MGH team investigated whether solid pressure exerted by proliferating cancer cells could compromise blood supply in the same way that stepping on a hose cuts off the flow of water. Using human tumors implanted in mice, the researchers administered diphtheria toxin, which kills tissue from humans but not from mice, to selectively destroy cancer cells. Analysis of the toxin-treated tumors found that both blood vessels and lymphatic vessels looked much more open than did vessels from untreated tumors, which were largely collapsed. Although the treated blood vessels appeared to be functioning nearly normally, however, treated lymphatic vessels were not functional.

"Some of the new questions we need to investigate are why decompressed lymphatics do not function, what role vessel decompression may play in tumor growth and metastasis, and how we can use vessel decompression to improve cancer treatment," says Jain. Co-authors of the article are Timothy Padera, Brian Stoll, PhD, Jessica Tooredman, Diane Capen, and Emmanuelle di Tomaso, PhD, all
of the Steele Laboratory.