Researchers have identified a growth factor, called EGFL6, that appears to promote ovarian cancer growth and spread in both cell lines and mouse models, according to a study published in Cancer Research.
The study, “EGFL6 Regulates the Asymmetric Division, Maintenance, and Metastasis of ALDH+ Ovarian Cancer Cells,” suggests that blocking this protein has the potential to reduce cancer growth in ovarian cancer patients and prevent it from metastasizing.
In recent years, studies have increasingly supported the role of cancer stem cells in tumor growth, which work by reproducing themselves and giving rise to differentiated cancer cells that fuel the tumor, much like normal stem cells do in healthy tissues.
However, little is known about the factors that regulate the asymmetric division of cancer stem cells. Given the role of EGFL6 in stem cell proliferation and differentiation in a variety of biological systems, the researchers sought to examine if EGFL6 also played a part in the proliferation of ovarian cancer stem cells.
They found that triggering EGFL6 expression in ovarian cancer cells led to a two- to three-fold increase in the rate of cell proliferation in both cell lines and ovarian cancer mouse models. When the researchers impaired the production of this protein, however, the tumor grew nearly four times more slowly.
Using microfluidic chambers to look into individual cells, the researchers found that EGFL6 was playing a part in the asymmetric division of cancer stem cells. Without EGFL6, a cancer stem cell could not properly divide into a new cancer stem cell and a differentiated daughter cell.
“What this means is that the stem cell population remains stable. But the daughter cells, which can have a burst of growth, multiply and allow the cancer to grow,” Ronald J. Buckanovich, MD, PhD, a professor of hematology/oncology and gynecologic oncology at the University of Michigan Medical School, said in a press release.
But importantly, EGFL6 wasn’t involved only in cancer stem cell proliferation; it also induced cancer stem cell migration. When this growth factor was added into the bloodstream of ovarian cancer mouse models, their tumor was much more likely to metastasize.
Using a EGFL6 blocking antibody, the investigators found that inhibiting this protein was enough to reduce the cancer stem cell pool by 35%, which led to a significant reduction in tumor growth. Also, the development of metastasis was impaired with EGFL6 inhibition.
Together, the findings suggest that inhibiting EGFL6 with a blocking antibody may be a promising therapeutic approach for women with advanced ovarian cancer, preventing the cancer from growing and spreading.
“The bigger implication is for women at high risk of ovarian cancer,” said Buckanovich. “These patients could be treated before cancer develops, potentially blocking cancer from developing or preventing it from spreading. If cancer did develop, it could be diagnosed at an early stage, which would improve patient outcomes.”
The next step is to develop an antibody that is suitable to be used in humans, and to test it further in clinical settings.