Jefferson Scientists Find Promising Weapon Against Cancer
A natural substance in the cell’s outer hull may actually hold a key to stopping tumor growth.
Renato V. Iozzo, M.D., professor of pathology and cell biology, at Jefferson Medical College, Thomas Jefferson University, Philadelphia, believes that the substance, called decorin, is actually a natural cancer fighter built into the cell.
Recently, he and his colleagues reported in the Journal of Clinical Investigation that decorin suppresses tumor cell growth by activating a specific protein growth factor called epidermal growth factor (EGF) receptor. According to Dr. Iozzo, decorin inhibits tumor cell growth by disrupting the cancer cell’s life cycle. They found that EGF and decorin converge to regulate the cell cycle through a common biochemical pathway, which ultimately suppresses tumor cell growth. "We found that we could replace decorin with EGF, proving we could displace one molecule with another," he notes.
He and his co-workers previously discovered that decorin also causes production of a protein, p21, which also can arrest cell growth.
In theory, he says, scientists could develop an animal model to study decorin’s action in which high levels are provided to tumor cells "either systemically or by gene therapy in hopes of retarding tumor growth." Ultimately, he notes, "we’d like to identify the mechanism of tumor cell suppression."
But harnessing decorin’s anti-tumor properties is not easy, and Dr. Iozzo hopes to understand how decorin works. He discovered several years ago that decorin, a cell protein, and specifically, a protoglycan, is increased in the matrix surrounding tumor cells. Decorin is a naturally occurring substance in the connective tissue where, among other roles, it helps regulate cell growth by interacting with growth factors and collagen.
Dr. Iozzo and his co-workers previously showed in laboratory experiments that decorin inhibits the growth of tumor cells. Dr. Iozzo’s group also unraveled the genetic makeup of decorin, and then selectively engineered--"transfected"--colon carcinoma cells with decorin DNA. In the test tube, the cancer cells didn’t grow as well, and formed smaller tumor colonies than nonengineered cancer cells from the same parent cancer. The new cancer cells did not generate tumors at all when they were injected into mice that lacked immune systems. He found similar results in melanoma, osteosarcoma, and colon cancer. "It may be a biological response to tumors, and much of the cell may wall off tumor cells," he explains.
Dr. Iozzo and his colleagues found that decorin is also increased in the tissue surrounding colon cancer cells. He suspects that "this may be an effort on the part of the decorin molecule produced by the normal cells to control the proliferation of cancerous cells in the colon."
Dr. Iozzo believes the work opens the possibility of therapeutic interventions in human colon cancer, and possibly other related types of cancers, using naturally occurring decorin to inhibit cancer growth.
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