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Washington, D.C. — Researchers at Lombardi Cancer Center at Georgetown University Medical Center have designed a method of "fingerprinting" molecules involved in helping cancer cells spread to distant organs, and have used this method to identify a protein that may enable the spread of colon cancer to the liver. Their findings will be presented at the 92nd annual meeting of the American Association for Cancer Research, to be held March 24-28 in New Orleans.
It is already known that certain types of cancer are more likely to spread to certain organs—for example, colon cancer frequently spreads to the liver, and prostate and breast cancers are more likely to spread to bone marrow than to other organs. It is this metastasis that makes cancer so lethal, but the molecular mechanism behind metastasis is still poorly understood.
Justinian Ngaiza, MD, PhD, a clinical fellow in hematology/oncology, working in the laboratory of Anton Wellstein, MD, PhD, is exploring the possibility that the "fingerprint" protein they have identified, "PA28 alpha," may be a cause of the colon-liver connection and thus a key to a deeper understanding of metastasis.
"Although this finding is in only the very earliest stages and not ready for human trials, the initial evidence is compelling," Ngaiza said. "The discovery of proteins that cause cancer to spread could one day lead to tests that would detect cancer much earlier than is now possible, and to treatments that would eradicate cancer from the body entirely."
Ngaiza’s experiments, conducted with his colleagues at Lombardi, involved injecting mice with a large collection of molecules derived from a type of colon cancer, and then identifying the specific molecules that spread to the liver. After isolating approximately 25 molecules that had spread to the liver, scientists then injected these molecules individually into subsequent mice.
Of the two molecules that accumulated most specifically in the liver, it was PA28 alpha that was found most abundantly in the liver and that was most liver-specific—that is, it was drawn more strongly to the liver than were the other molecules.
Lombardi researchers will conduct further tests to determine more precisely the role of PA28 in metastasis. These tests will include removing PA28 alpha from one type of colon cancer cell and injecting the cells into mice. If Ngaiza’s hypothesis is correct, the mice will develop colon cancer, but the cancer would not spread to the liver.
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