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PITTSBURGH, PA – Researchers at the University of Pittsburgh have made a significant breakthrough in understanding the origins of high-grade serous ovarian cancer (HGSOC), the most lethal form of ovarian cancer. Their findings, published in the journal Cancer Discovery, pinpoint a specific subset of progenitor cells within the fallopian tube’s supportive tissue, or stroma, as a critical trigger for the disease.
This discovery of these high-risk mesenchymal stem cells (MSCs) could revolutionize approaches to prevention and early detection of HGSOC, which claims the lives of over 12,000 women annually in the United States.
“Ovarian cancer is the leading cause of death from gynecologic cancer in the Western world, but we currently have no way to detect it early and no prevention strategies apart from surgical castration, which is only indicated in high-risk women,” stated Dr. Lan Coffman, co-senior author of the study and associate professor of malignant hematology and medical oncology at the Pitt School of Medicine.
HGSOC originates in the fallopian tubes, where healthy epithelial cells transform into precancerous lesions known as serous tubal intraepithelial carcinoma (STIC). The researchers focused on the stroma, the non-cancerous tissue surrounding these lesions, to understand why these transformations occur.
Contrary to previous research that primarily focused on epithelial cells, Dr. Coffman and her team discovered that high-risk MSCs, found within the stroma, play a crucial role in cancer initiation. These cells, more prevalent in women with higher risk factors such as older age and BRCA gene mutations, were found to reprogram healthy epithelial cells into cancerous ones when introduced into fallopian tube organoids.
“High-risk MSCs promote DNA damage in epithelial cells and then help those mutated cells survive,” Dr. Coffman explained. “It’s the perfect storm for cancer initiation.”
Further investigation revealed that these high-risk MSCs exhibit a loss of the antioxidant AMP kinase, leading to increased levels of the protein WT1, which drives DNA damage. Additionally, these MSCs were found to promote tumor growth and increase resistance to chemotherapy.
This groundbreaking research marks the first time that stromal changes in the fallopian tube have been identified as a causative factor in ovarian cancer initiation. The findings also suggest potential avenues for intervention, such as utilizing existing drugs that upregulate AMP kinase to prevent or reverse early stromal changes.
Furthermore, the compounds secreted by high-risk MSCs, which are detectable in the bloodstream, could serve as biomarkers for early-stage ovarian cancer detection, addressing the current lack of effective early detection methods.
“This is the first report that stromal changes in the fallopian tube actually have a causative role in ovarian cancer initiation,” said Coffman. “It also points to a path where we might be able to intervene.”
Disclaimer: This article is based on information provided in a recent research study. Further research and clinical trials are necessary to validate these findings and translate them into effective prevention and treatment strategies. The information provided here should not be considered medical advice. Consult with a healthcare professional for any health concerns or before making any decisions related to your health or treatment.
