Ovarian cancer stem cells stimulated by common treatment
Chemotherapy drugs designed to kill tumors may actually encourage ovarian cancer by stimulating the growth of cells that give rise to the malignancy, a new study finds.
“It was quite a surprise, actually, that chemotherapy could stimulate growth,” says Kenneth Nephew, a cancer biologist at the Indiana University School of Medicine in Bloomington, who was not involved in the new work. “When clinicians see this paper it may raise a few eyebrows.”
Researchers led by Patricia Donahoe and Xiaolong Wei of Massachusetts General Hospital and Harvard Medical School found that the common chemotherapy agent doxorubicin actually encourages the growth of ovarian cancer stem cells. The immature cells make up less than 1 percent of an ovarian cancer, but just a few left behind after surgery can reestablish a tumor.
But the study, published online the week of January 23 in the Proceedings of the National Academy of Sciences, also offers hope. The researchers found that a protein called Müllerian inhibiting substance, or MIS, halts growth of cancer stem cells. Made by male fetuses and boys until puberty, the protein reverses the growth of tissues that would otherwise develop into fallopian tubes.
MIS treatment might be combined with chemotherapy (which does kill most mature ovarian cancer cells) to stop growth of all the cancer cells, says Charles Landen, a gynecologic oncologist at the University of Alabama at Birmingham. Since humans naturally produce the potential anti-stem cell treatment, it would probably be safe to use in a clinical setting, he says.
Such therapy is still a long way off, says Donahoe. The researchers are able to produce only enough Müllerian inhibiting substance for use in a laboratory setting. Making enough of the protein to test in clinical trials will probably require a commercial partner.
Other researchers have identified different types of ovarian cancer stem cells, but Donahoe and her colleagues “have defined what may be the most aggressive subset of tumor cells,” says Landen.
It’s not clear if the MIS protein can stop all types of ovarian cancer stem cells.
K. Meirelles et al. Human ovarian cancer stem/progenitor cells are stimulated by doxorubicin but inhibited by Mullerian inhibiting substance. Proceedings of the National Academy of Sciences. Published online the week of January 23, 2012. doi:10.1073/pnas.1120733109.