Title Extended passaging of the SKOV3 ovarian cancer cell line leads to two phenotypically different strains
Authors Žymantaitė, Eglė ; Gabrielaitė, Miglė ; Pašukonienė, Vita ; Mlynska, Agata
DOI 10.1242/dmm.052451
Full Text Download
Is Part of Disease Models & Mechanisms.. Cambridge : The Company of Biologists. 2025, vol. 18, iss. 8, art. no. dmm052451, p. 1-12.. ISSN 1754-8403. eISSN 1754-8411
Keywords [eng] cancer cell lines ; ovarian cancer ; clonal evolution ; late passaging ; SKOV3
Abstract [eng] Continuous passaging of cancer cell lines can drive phenotypic and genotypic divergence, potentially compromising the reliability of such models. In this study, we show that two late-passage strains (S1 and S2) of ovarian cancer cell line SKOV3, although authenticated via short tandem repeat (STR) profiling as identical, exhibit substantial differences in morphology, transcriptomic signatures, ability to form 3D cultures and chemotherapeutic responses. Notably, S1 formed compact 3D spheroids and exhibited enhanced epithelial-mesenchymal transition (EMT) pathway activity, whereas S2 displayed a more proliferative, MYC-driven phenotype with larger spheroid structures requiring higher seeding densities. Transcriptomic analysis revealed pathways associated with hypoxia, EMT and angiogenesis in 3D culture, highlighting the complexity introduced by dimensionality in tumour modelling. Critically, S1 showed higher sensitivity to doxorubicin than S2 (IC50 of 0.12 µM versus 1.28 µM, P=0.0001), indicating how clonal evolution can confound drug-response assays. Ultimately, our findings suggest that although STR profiling remains essential for cell line authentication, functionally distinct subpopulations can arise and coexist within the same culture, and their isolation may reveal divergent phenotypes that compromise reproducibility in preclinical cancer research.
Published Cambridge : The Company of Biologists
Type Journal article
Language English
Publication date 2025
CC license CC license description