Cancer Stem Cells engage Normal Stem Cells to promote Ovarian Cancer

The growth of cancer stem cells is promoted by a type of normal stem cell that stimulates ovarian cancer, as discovered by researchers at the University of Michigan Comprehensive Cancer Center.

Tumor growth and proliferation is driven by a small number of cancer stem cells within the tumor. Conventional cancer treatments are most often unsuccessful because they fail to kill these cells.

An online study published in the Journal of Clinical Investigation revealed that researchers examined ovarian tissue for mesenchymal stem cells. These are normal cells that occur throughout the body and can differentiate into specialized cells such as fat, bone, or cartilage.

Many scientists speculate that mesenchymal stem cells may help fight cancer because they are known to assist in the wound healing process. In this study, researchers observed that mesenchymal stem cells in ovarian tumors were different from those in healthy ovaries; further, cancer was promoted by mesenchymal stem cells in the ovarian tumors.

Study author and assistant professor of internal medicine and of obstetrics and gynecology at the U-M Medical School, Ronald Buckanovich, M.D., Ph.D., says that “Cancer is very good at tricking the mesenchymal stem cells into doing what the cancer likes. The cancer takes the cells hostage and uses them to promote the cancer’s growth.”

The researchers examined mesenchymal stem cells by using mouse models and human tissue samples of both normal ovaries and cancer-associated ovaries. They observed that cancer-associated mesenchymal stem cells caused an increase in tumor size primarily by escalating the number of cancer stem cells.

Researchers also noticed a type of protein called BMP2 that was rampant in cancer-associated mesenchymal stem cells. In normal cell function, the master regulatory protein BMP2 is carefully regulated. Compared with normal mesenchymal stem cells, researchers found more than three times the amount of BMP2 in cancer-associated mesenchymal stem cells. A proliferation of cancer stem cells was observed when BMP was added to cancer cells.

The researchers then found that mesenchymal stem cell activation of cancer stem cells can be blocked by using a known BMP inhibitor called Noggin. Buckanovich says that “High doses of Noggin might not be tolerated in humans.” He added that “Our next step is to figure out how to target Noggin directly to the vascular niche where the mesenchymal stem cells and cancer stem cells live. This would allow us to make it safer to use Noggin as a potential treatment for ovarian cancer.”

Before this research can be advanced to clinical trials in patients, it must be continued in the laboratory. Meanwhile, the U-M Comprehensive Cancer Center plans on testing other therapies that are aimed at fighting ovarian cancer stem cells by launching two new clinical trials within the next year.

For information, contact the Cancer AnswerLine at 800-865-1125.

Notes:

Ovarian cancer statistics: 21,880 Americans will be diagnosed with ovarian cancer this year and 13,850 will die from the disease, according to the American Cancer Society

Additional authors: Karen McLean, Yusong Gong, Junjung Choi, Ning Deng, Kun Yang, Shoumei Bai, Lourdes Cabrera, Evan Keller, Laurie McCauley and Kathleen R. Cho, all from U-M

Funding: Damon Runyon Cancer Research Foundation, National Institutes of Health

Disclosure: None

Reference: Journal of Clinical Investigation, doi:10.1172/JCI45273

Source:
Nicole Fawcett
University of Michigan Health System