Browsing by Author "Suominen, Lasse"

Ovarian cancer is the third most common gynecological cancer worldwide. Most ovarian cancers are high-grade serous ovarian cancers (HGSOC). HGSOC is usually diagnosed after metastasis due to lack of early symptoms. The prognosis is poor due to the lack of symptoms and chemoresistance that often develops. Stromal cells in cancers can both restrict and promote the tumor progression as well as modulate cancer cells’ response to therapy. Knowledge of differences in stromal cell subpopulations between different metastatic sites as well as of how chemotherapy affects the subpopulations is lacking, making developing new treatments targeting the tumor stroma difficult. The aims of this study were to characterize the stromal cell populations in HGSOC tumors and in healthy tubal tissue and to analyze the differences in subpopulations between different tumors. We used single-cell RNA-sequencing to characterize the stromal subpopulations in sixty-five tumor samples collected from different metastatic tissues both before and after chemotherapy and in five healthy tubal samples. We found eighteen stromal subpopulations in HGSOC and healthy tubal tissues. Ten subpopulations were cancer-associated fibroblasts including five previously characterized subtypes and five novel subtypes. Additionally, we found for example mesothelial cells, endothelial cells, and ovarian stromal cells. We demonstrated that certain cell populations are enriched in different metastatic tissues. Additionally, we demonstrated that stromal subpopulations differ between tumors collected before and after chemotherapy. Our results show that there are significant systematic differences in stromal subpopulations between HGSOC tumors from different conditions. Understanding these differences together with the knowledge of how these cells affect the tumor progression will enable the development of treatments targeting the tumor stroma.