SKOV3 Cell Line Insights: Key Morphological and Genetic Traits

SKOV3 is a widely used ovarian cancer cell line that has significantly contributed to research on tumor biology, drug resistance, and therapeutic development. Derived from human ovarian adenocarcinoma, it serves as a valuable model for studying ovarian cancer at both cellular and molecular levels.

Its unique characteristics distinguish it from other ovarian cancer cell lines, shaping its applications in experimental studies. Understanding these traits highlights its relevance in oncological research.

Morphological Traits

SKOV3 cells exhibit an epithelial-like morphology, characterized by a polygonal shape and an adherent growth pattern. Unlike structured epithelial cells that form tight junctions, SKOV3 cells display a loosely associated arrangement, growing in clusters with irregular adhesion. This feature reflects their mesenchymal-like tendencies, contributing to their migratory and invasive capabilities. The cytoplasm appears abundant and granular under phase-contrast microscopy, while the nuclei are relatively large with prominent nucleoli, indicative of active transcription.

Their cytoskeletal organization further defines their morphology. Immunofluorescence studies reveal a well-developed actin cytoskeleton with stress fibers supporting motility. Vimentin, a mesenchymal marker, is frequently expressed alongside cytokeratins, highlighting their hybrid epithelial-mesenchymal phenotype. This dual expression aligns with their plasticity, a trait linked to resistance to anoikis, a form of programmed cell death triggered by detachment from the extracellular matrix.

Another defining feature is their ability to form spheroids under non-adherent conditions. When cultured in suspension or three-dimensional matrices, SKOV3 cells aggregate into compact, rounded structures, mimicking peritoneal tumor nodules observed in ovarian cancer metastasis. These spheroids exhibit increased resistance to chemotherapeutic agents, a property extensively studied in drug response assays. The ability to transition between adherent monolayers and spheroid formations underscores their adaptability, making them a relevant model for tumor progression research.

Genetic Characteristics

SKOV3 cells exhibit a highly aneuploid genome with extensive chromosomal instability, a hallmark of high-grade ovarian carcinomas. Karyotypic analyses reveal frequent gains in chromosomes 3, 7, and 20, alongside losses in chromosome 13. These alterations contribute to dysregulated gene expression, affecting pathways related to proliferation, apoptosis, and drug resistance. Comparative genomic hybridization studies have identified amplifications in regions harboring oncogenes such as MYC and KRAS, which drive uncontrolled growth.

A defining genetic feature of SKOV3 cells is the absence of functional TP53, a tumor suppressor gene frequently mutated in ovarian cancer. Unlike many ovarian carcinoma cell lines that harbor missense mutations leading to dysfunctional p53 protein, SKOV3 cells exhibit a near-complete loss of TP53 expression due to a homozygous deletion. This deficiency impairs apoptosis in response to DNA damage, conferring a survival advantage under genotoxic stress. Studies have shown that reintroducing wild-type TP53 restores apoptotic sensitivity, underscoring its role in tumor suppression and therapeutic response.

Beyond TP53, SKOV3 cells display aberrations in pathways regulating cell adhesion and motility. Mutations and copy number variations in genes such as CDH1 (E-cadherin) and ZEB1 contribute to epithelial-to-mesenchymal transition (EMT), enhancing invasiveness and metastatic potential. Loss of E-cadherin disrupts intercellular junctions, facilitating detachment and dissemination. Concurrently, upregulation of mesenchymal markers like SNAI1 and TWIST1 promotes a migratory phenotype, aligning with their aggressive behavior in invasion assays.

Growth Behavior

SKOV3 cells exhibit a robust proliferative capacity, growing in monolayers with a relatively short doubling time. Under optimal culture conditions, they maintain an exponential growth phase, with doubling times typically ranging from 24 to 36 hours, depending on media composition and serum concentration. Their lack of strong contact inhibition allows them to form dense, overlapping colonies, mirroring uncontrolled tumor expansion in vivo.

Nutrient availability and extracellular conditions significantly influence their proliferation. SKOV3 cells demonstrate adaptability to varying glucose levels, maintaining growth even under glucose-deprived conditions, though at a reduced rate. This metabolic flexibility is indicative of altered energy utilization, a feature common in cancer cells that rely on both oxidative phosphorylation and glycolysis for ATP production. Additionally, they exhibit resilience to hypoxic environments, where oxygen supply is limited. Hypoxia-inducible factors (HIFs) are upregulated under low-oxygen conditions, promoting angiogenesis-related gene expression and sustaining proliferation.

Their ability to transition between adherent and suspension growth states further distinguishes their behavior. In low-attachment conditions, SKOV3 cells readily form multicellular aggregates, enhancing resistance to apoptotic signals. This spheroid formation is particularly relevant in chemoresistance studies, as three-dimensional growth conditions better reflect tumor architecture and drug penetration challenges. Unlike strictly adherent cell lines, SKOV3 cells survive detachment-induced stress, contributing to their ability to disseminate and establish secondary tumor sites.

Distinguishing Features From Other Ovarian Cell Lines

SKOV3 differs from other ovarian cancer cell lines due to its unique combination of genetic alterations, phenotypic plasticity, and adaptability. Unlike A2780, which is often used as a model for cisplatin-sensitive ovarian cancer, SKOV3 exhibits pronounced resistance to platinum-based chemotherapies, a trait linked to its TP53 deficiency. This resistance makes SKOV3 a preferred model for treatment-refractory ovarian cancer, particularly in studies of apoptosis-independent therapeutic strategies.

Compared to OVCAR-3, which closely resembles high-grade serous ovarian carcinoma (HGSOC) with strong epithelial morphology and E-cadherin expression, SKOV3 displays a more mesenchymal-like phenotype with reduced cell-cell adhesion. This distinction is significant, as SKOV3’s diminished epithelial characteristics contribute to its migratory and invasive tendencies, making it a valuable tool for studying epithelial-to-mesenchymal transition (EMT) and metastasis. Additionally, while OVCAR-3 retains estrogen and progesterone receptor expression, SKOV3 lacks hormone receptor responsiveness, limiting its utility in hormone-driven ovarian cancer research but enhancing its relevance for hormone-independent tumor progression studies.

Common Observations In Experimental Studies

SKOV3 cells have been extensively utilized in cancer research, with recurring observations shedding light on their behavior under different conditions. One of the most consistent findings is their pronounced resistance to chemotherapy, particularly platinum-based agents like cisplatin and carboplatin. Unlike many ovarian cancer cell lines that undergo apoptosis following DNA damage, SKOV3 cells often survive treatment due to their TP53 deficiency. This resistance has been linked to increased activation of the PI3K/AKT signaling cascade. Studies have shown that pharmacological inhibition of AKT can sensitize SKOV3 cells to chemotherapy, suggesting targeted therapies may be more effective than traditional cytotoxic agents in overcoming drug resistance.

Their ability to form spheroids in suspension cultures has led to important discoveries regarding tumor progression and metastasis. Spheroid formation enhances cell-cell interactions that contribute to survival and chemoresistance, mimicking ovarian cancer cells in malignant ascites. Experimental studies have demonstrated that SKOV3 spheroids exhibit increased expression of stemness-associated markers such as ALDH1 and CD44, indicating a potential enrichment of cancer stem-like cells. This property makes them a valuable model for investigating tumor recurrence mechanisms, as cancer stem-like populations are often implicated in disease relapse. Additionally, SKOV3 cells display heightened migratory and invasive capabilities in transwell assays, further supporting their role in studying metastatic dissemination.