Defeat Tumor Cells By Inhibiting Healthy Cells

Defeating malignant tumors by attacking healthy cells seems like an unusual strategy, but scientists at Washington University School of Medicine in St. Louis have shown the strategy to be effective against leukemia/lymphoma in mice.

Led by Katherine N. Weilbaecher, M.D., assistant professor of medicine, the research group found that inhibiting normal bone-maintenance cells called osteoclasts not only prevented the mice's cancer from spreading to their bones, it also slowed the growth of tumors in the body's soft tissues.

"Tumor cells can mutate to overcome the therapys we use, but normal body cells won't," says Weilbaecher, an oncologist with the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. "And since cancer cells depend on the normal cells in our body for their survival, we can sometimes get at them by targeting more vulnerable host cells. In this case, by going after osteoclasts, we were able to affect tumor cells."

The mice used in the study were developed in the laboratory of Lee Ratner, M.D., Ph.D., professor of medicine, of molecular microbiology and of pathology and immunology. The Ratner group introduced a gene called Tax into the mice's genome. Having the Tax gene makes the mice very susceptible to T-cell leukemia/lymphoma, a blood cancer that also forms soft-tissue tumors and metastasizes to invade bones.

The Tax gene comes from human T-cell leukemia virus type 1 (HTLV-1), a virus that infects 10 to 20 million people worldwide and causes an aggressive form of adult T-cell leukemia/lymphoma in about 5 percent of infected people.

When the Tax-transgenic mice develop this cancer, their tumor cells secrete factors that activate osteoclasts. Osteoclasts are one of two types of cells that participate in the normal renewal of bone throughout an organism's lifetime - osteoclasts break down old bone and osteoblasts build up new bone to maintain bone health.

By activating osteoclasts, the mice's tumors cause excessive bone breakdown, and their bones develop holes that allow malignant cells to enter and proliferate.

When the research group inhibited osteoclast activity, they saw that the mice were protected from tumor-associated bone destruction and from bone tumors. But interestingly, the mice also developed fewer tumors in other areas of the body. Their tumors grew more slowly, and the mice survived longer than mice without the Tax gene.



Source: Washington University in St.Louis - School of Medicine

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