Rewriting the Origins of Ovarian Cancer: The Role of Stromal Support Cells
Ovarian Cancer is often found too late, but the multi-disciplinary team spanning clinical experts at the University of Pittsburgh (UPitt) and their collaborators has recently discovered new early detection and prevention strategies for ovarian cancer.
Co-Seniors Drs. Lan G. Coffman and Huda I. Atiya thoughtfully transform early detection and prevention strategies with their recently published study, titled “Aged and BRCA-Mutated Stromal Cells Drive Epithelial Cell Transformation.” With this study came the new notion that cancer could start from neighboring cells at risk, and not just from the mutations of faulty cells.
The study focuses on two main types of cells. Fallopian Tube Epithelial (FTE) cells, or the cells that line the inside of the fallopian tubes, and stromal cells. Stromal cells are support cells found in tissues within the body specifically in the Fallopian tubes. FTE cells are typically laid against a backdrop of supporting stromal tissue.
In this study, a unique group of stromal cells within the fallopian tubes called high-risk mesenchymal stem cells (hrMSCs), seems to play a critical role in early cancer development. These (hrMSCs) cells are primarily found in mature women, or women who possess the BRCA1 or BRCA2 genetic mutations.
Mesenchymal Stem/Stromal Cells (MSCs) are normally reparative. Still, certain MSCs, the “high risk” MSCs, or (hrMSCs) adopt harmful behaviors in older women, or women carrying the BRCA 1 or BRCA 2 mutations. These cells release lipid aldehydes, which are toxic chemicals that damage nearby epithelial (surface) cells. These stromal cells are important because until now, the spotlight has been mostly held on epithelial cell mutations, but this study reveals that the stromal cells might also initiate transformation into cancer cells.
Within this study, it states that FTE cells can evolve into Serous Tubal Intraepithelial Carcinoma (STIC) lesions. These lesions are the earliest visible precursor to High-Grade Serious Ovarian Cancer (HGSOC). These processes from the FTE and (hrMSCs) behavior, create a “fertile ground” for cancer to grow, even before a tumor forms.
The team led by Drs. Coffman and Atiya at UPitt/UPMC Hillman Cancer Center and Magee-Women’s Research Institute revealed their approach to observing this phenomenon. The team began with profiling. They collected the two different cell types that reside in the lining of the fallopian tubes (FTE and stromal MSCs) from healthy and high-risk women who were either older or carriers of the BRCA1/2 mutations.
Then the scientists conducted functional tests that involved examining and analyzing co-cultured MSCs with patient-derived organoids and monitoring FTE cell behavior. They utilized animal studies and implanted cells into mice for malignant transformation. They utilized tools such as spatial transcriptomics, flow cytometry, in vitro-tumor assays, and mechanistic knock-in/out models, to draw conclusions.
The doctors’ study revealed the role stromal cells play in transforming the fallopian epithelial cells into cancer. It also discovered that cancer risk is based upon more factors than just good or bad genetics or cells. The implications of this study imply that cancer risk can also be affected by faulty neighboring cells.
This study also implicates new avenues for prevention, making room for research that provides a more modern strategy for battling cancer by targeting or protecting against harmful stromal cell behavior. These findings will influence how researchers design future cancer therapies, constructing treatments that not only kill cancer cells but also stabilize the surrounding tissue environment. Ultimately, scientists discovered that stromal cells might be causing cancer to start, but with this knowledge, doctors and scientists alike can change how we look at early cancer detection and prevention.