Article published in esteemed journal Progress in Lipid Research.

Gjorgoska Marija, Lanišnik Rižner Tea, From fallopian tube epithelium to high-grade serous ovarian cancer: A single-cell resolution review of sex steroid hormone signaling. Progress in Lipid Research 2024; 96:101302. doi: https://doi.org/10.1016/j.plipres.2024.101302 (IF = 14)

The first author of this article is Asst. Marija Gjorgoska, M.Sc. neuro. sci., M.Sc. mol. function. biol., assistant and PhD student at the Institute of Biochemistry and Molecular Genetics UL MF. This article is the result of her work within the program P3-0449 Translational Molecular Endocrinology for Women's Health.

High-grade serous ovarian cancer (HGSOC) is the most lethal form of ovarian cancer, typically diagnosed at advanced stages. The early molecular mechanisms driving its development remain poorly understood, posing significant challenges to the creation of early diagnostic strategies. In this article the authors delve into the molecular mechanisms of steroid hormone signaling throughout the decades-long progression of HGSOC precursor lesions originating in the secretory epithelial cells of the fallopian tubes, as well as in HGSOC itself.

The study integrates high-dimensional data from single-cell RNA sequencing to analyze hormone receptor and enzyme expression in cell populations of the fallopian tubes in healthy women, both before and after menopause, and in the HGSOC microenvironment. These atlases reveal that secretory epithelial cells and stromal populations in the fallopian tubes from healthy women express receptors for steroid hormones, as well as enzymes involved in the formation and inactivation of genotoxic estrogen metabolites. In cases where enzymatic balance is disturbed, the risk of secretory cell dysplasia and the formation of HGSOC precursor lesions increases. In HGSOC, epithelial cells express various HSD17B isoforms and steroid conjugation enzymes, suggesting a capacity to regulate levels of bioactive steroid hormones. These findings highlight that secretory cell populations in the fallopian tubes and epithelial cancer cells in HGSOC are particularly responsive to therapeutic agents targeting steroid hormone signaling. This understanding opens new avenues for the development of effective therapeutic strategies for HGSOC.