October 1, 1999

An MGH research team has discovered that a cellular growth factor called TGFß1 has a previously unsuspected role in regulating the growth of blood vessels associated with metastatic gallbladder cancer.

The study's results, appearing in the October issue of Nature Medicine, may someday lead to strategies to prevent the growth of metastases from gallbladder cancer, a serious problem in treatment of the disease.

In gallbladder cancer, metastases are few and very small as long as the primary tumor remains in place. But when the tumor is surgically removed – the only current treatment for the disease – metastases appear and grow quickly. As a result, only about 5 percent of patients having the surgery survive for five years or more.

In their animal study, the research team led by Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology, found that primary gallbladder tumors appear to suppress the growth of metastases and associated angiogenesis by producing TGFß1, known to be a cellular growth factor. "We were very surprised with this result," says Jain. "TGFß1 is what we call a pluripotent cytokine. It can have many different effects depending on the concentrations at which it is present, its location and other circumstances. Some studies have shown that it promotes angiogenesis. Finding that it can suppress angiogenesis in gallbladder cancer is provocative."

The paper's first author, Takeshi Gohongi, MD, a research fellow in the Steele Lab, adds, "This discovery may give us an opportunity to develop new postsurgical treatment protocols. If we can learn how to modulate TGFß1 levels after removal of the primary tumor, we may be able to prevent the rapid growth of metastases that proves fatal for so many of these patients."

The paper's co-authors include Dai Fukamura, MD; Yves Boucher, PhD; and Chae-Ok Yun, PhD, of the Steele Laboratory.