Protein pushes cancer cells to self-destruct
NEW YORK, Jan 03 (Reuters Health) - Researchers have found a protein that plays a key role in the body's naturally occurring cell suicide program, which is important for eliminating diseased, damage or aged cells.
The protein was found to be missing or damaged in at least some colon cancer cells, and restoring the protein--in laboratory studies--caused the cancer cells to self-destruct.
Dr. Atsushi Suzuki of Daiichi Pharmaceutical Co. in Tokyo, Japan, and associates hope the protein, known as SADS (for small-accelerator for death signaling), might be a potential way to treat colon cancer. They report their findings in the January issue of Nature Medicine.
SADS appears to work in concert with another protein, called Fas, which is known as the death receptor. SADS was found in a number of normal tissues in the body that routinely undergo rapid cell turnover, including the colon, the spleen and the small intestine.
When they tested cancer cells from seven patients with colon tumors, the researchers found that SADS protein was reduced or absent in four of the seven. In six of the patients, there were abnormalities in the gene for SADS.
Moreover, by artificially increasing SADS levels in colon cancer cells in the laboratory, the researchers were able to induce death in cells that already made Fas.
"We showed a possible involvement of SADS deletion in colon cancer," Suzuki told Reuters Health. "And we switched on cell death in colon carcinoma as a result of an exogenous expression of SADS. We believe SADS is one of the (factors involved in cancer development)."
The investigators found that SADS-expressing cells could induce the self-destruction in the SADS-deficient cells if they came into contact with one another. This suggests that it might be possible to treat colon cancer with some type of gene therapy that introduces a SADS-expressing gene into body cells, the authors conclude.
The findings represent a "substantial advance" in the understanding of the cell suicide mechanism, according to an editorial by Dr. Hiroshi Takahashi, who is now at Massachusetts General Hospital in Boston.
Takahashi also told Reuters Health, "Since SADS is expressed in a number of cell types, including liver, lung, lymphocytes (white blood cells) and small intestine, as well as colon, we expect that the downregulation of this molecule is involved in several cell types of cancer."
SOURCE: Nature Medicine 2001;7:26-27, 88-93.