In a recent publication, Northwestern Medicine scientists and collaborators at Purdue University proposed a new marker to identify ovarian cancer stem cells, which may lead to the development of a new class of drugs that could target those cells for eradication.
The study, published in Cell Stem Cell, proposes a method for targeting cancer stem cells through metabolic markers. While cancer stem cells are a small population of all cancer cells, they have the ability to initiate tumors and have been shown to be resistant to current therapies.
“When cancer stem cells persist and are not killed by standard treatments, they can repopulate and cause tumor relapse,” said Daniela Matei, MD, the Diana, Princess of Wales Professor of Cancer Research and professor of Obstetrics and Gynecology in the Division of Gynecologic Oncology and co-author on the study. “It is therefore very important to find out what the unique characteristics and vulnerabilities of cancer stem cells are and whether there are other modalities to target these cells other than traditional chemotherapy.”
Using a novel type of chemical imaging, called hyperspectral simulated Raman scattering microscopy, co-first-authors of the paper Junjie Li, PhD, and Salvatore Condello, PhD, research assistant professor of Obstetrics and Gynecology, analyzed the composition of fats inside individual living cells. This study represents the first application of this label-free imaging technology, developed by the Ji-Xin Cheng group at Purdue, to cancer stem cell biology.
“Lipid accumulation inside cancer cells has been known for decades. Nevertheless, how lipids function in cancer stem cells is not well understood. Chemical microscopy offers an elegant platform to decipher the role of cell metabolism in cancer development,” said co-author Ji-Xin Cheng, PhD, professor of Biomedical Engineering, professor of Chemistry, and scientific director of label-free imaging at Purdue University Discovery Park.
After comparing cancer stem cells and non-cancer stem cells using this imaging technique coupled with mass spectrometry, they discovered increased levels of unsaturated fatty acids in ovarian cancer stem cells. They also found increased levels of unsaturated lipids in ovarian cancer cells growing as spheres.
They identified that the enzyme fatty acid desaturase mediates the accumulation of increased unsaturated lipid levels and is critical for the maintenance and survival of cancer stem cells. Furthermore, Matei and her team demonstrated that the particular pathway through which this occurs is the NF-κB pathway. In addition, the team found metabolic inhibitors that could be used to eliminate the identified cancer stem cells, and might represent a novel cancer stem cell targeted therapy in the future.
In future research, Matei said she plans to continue to study the mechanisms through which unsaturated fatty acids contribute to stemness and tumor initiation. She is also working with collaborators to create imaging technology to observe cancer cells in tissues to better learn how tumor cells interact with their environment.
“We want to perfect and test these inhibitors of fatty acids with chemotherapy in animal models to bring better treatments to the clinic,” Matei said.
Matei is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
The research was funded by a VA Merit Award; National Cancer Institute grants CA198409 and CA182608; the Walther Cancer Foundation; and by a National Institutes of Health grant P30CA023168.
Credit: Northwestern Medicine scientists