Posted: Tuesday, January 21, 2025
Given the poor prognostic outcomes faced by patients with high-grade serous ovarian cancers, efforts have been dedicated to increasing the understanding of disease pathology in hopes of developing novel strategies to improve diagnosis and treatment, according to a study published in Molecular Therapy Oncology. Daniela Ungureanu, PhD, of the University of Oulu, Finland, and colleagues identified distinctions in the phenotypic characteristics of the malignant ovarian cell subtypes that may help guide additional studies to develop effective treatment options for this patient population.
Two immortalized cell lines, human ovarian surface epithelium (HOSE)1C and HOSE2C, were compared with representative high-grade serous ovarian cancer cells to analyze their cellular heterogeneity. In addition, single-cell RNA sequencing was used to mimic the normal and tumorlike microenvironments. Cell lines were subjected to various biochemical assays, including immunofluorescence, immunoblotting, drug sensitivity and resistance testing, and cell painting.
The study authors revealed that the HOSE1C and HOSE2C cell lines were associated with a stromal phenotype, compared with the previous belief that they were epithelial cells. Furthermore, the HOSE1C and HOSE2C cell lines demonstrated differences in their responses to transcription factors in the tumor microenvironment. HOSE1C was responsive to STAT1, whereas HOSE2C was responsive to GREM1. Moreover, the high-grade serous ovarian cancer cells showed selective activation of ERK/MEK targeted inhibitors compared with HOSE1C and HOSE2C cells.
“The fact that HOSEs cells were sensitive to many drug classes suggests that the specificity and cytotoxicity of anticancer drugs should be carefully analyzed using representative nonmalignant and malignant cellular models,” suggested the study authors.
Disclosure: The study authors reported no conflicts of interest.