In a groundbreaking study, researchers from the University of Pittsburgh have identified a subset of progenitor cells within the fallopian tube stroma that could trigger high-grade serous ovarian cancer (HGSOC). This discovery, published in Cancer Discovery, sheds light on how these high-risk mesenchymal stem cells (MSCs) transform healthy epithelial cells into precancerous lesions. The findings may lead to improved prevention and early detection strategies for HGSOC, which claims over 12,000 lives annually in the U.S.

Exploring the Origins of Ovarian Cancer

In an innovative research endeavor, scientists focused on the supportive tissue of the fallopian tubes where HGSOC is believed to originate. Through their investigation, they uncovered a specific type of progenitor cell—high-risk MSCs—that play a pivotal role in cancer initiation. These cells were found to be more prevalent in women at higher risk for ovarian cancer, such as those with BRCA gene mutations or advancing age. When introduced into organoids derived from patient fallopian tube tissue, these high-risk MSCs induced the transformation of healthy epithelial cells into cancerous ones. The study also revealed that high-risk MSCs promote DNA damage and enhance resistance to chemotherapy drugs by altering antioxidant levels and increasing protein production linked to DNA damage.

This revelation marks the first evidence that changes in the fallopian tube stroma actively contribute to ovarian cancer development. By understanding this mechanism, researchers hope to develop interventions using existing drugs that regulate antioxidant levels, potentially preventing early stromal changes leading to cancer. Moreover, compounds secreted by high-risk MSCs might serve as biomarkers for early-stage ovarian cancer, addressing the current lack of effective detection methods.

A team of experts, including Geyon Garcia, Taylor Orellana, Grace Gorecki, Leonard Frisbie, Roja Baruwal, Swathi Suresh, Ester Goldfeld, Ian MacFawn, Ananya Britt, Macy Hale, Brian Isett, Nadine Hempel, Riyue Bao, Ronald Buckanovich, Toren Finkel, T. Rinda Soong, Tullia Bruno, and Huda Atiya from Pitt and UPMC, contributed to this research alongside collaborators from Van Andel Research Institute and Penn State University. Funding was provided by Tina’s Wish, the Department of Defense, and the National Institutes of Health.

With this new understanding of the biological processes underlying ovarian cancer formation, there is optimism for better patient outcomes through targeted prevention and detection strategies.

Ovarian cancer remains a formidable challenge due to its late detection and limited preventive measures. This research underscores the importance of exploring the complex interplay between different cell types in cancer initiation. By targeting high-risk MSCs, we may unlock pathways to intervene earlier in the disease process, offering hope for reducing mortality rates associated with this devastating condition.