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Updated: Jan 15, 2026
Preparation of Mitochondria from Ovarian Cancer Tissues and Control Ovarian Tissues for Quantitative Proteomics Analysis
Published on: November 18, 2019
Targeting mitochondrial translation and OXPHOS in high-grade serous ovarian carcinoma eliminates stem-like cells
Aravindan Narayanan1, Souvik Guha1,2, Avinash Mali1
1BRIC-National Centre for Cell Science, Savitribai Phule Pune University, Pune, India.
Abstract:
Ex vivo stem cell self-renewal and maintenance is supported by absence of serum-derived mitogens. In the present study, we sought to elucidate the proteomes of stem-like cells grown in serum-free media across a panel of high-grade serous ovarian cancer cell lines, which encompass a gradient from epithelial, intermediate and mesenchymal cell phenotypes to recapitulate the heterogeneity of the disease. MaxQuant-based label-free quantification of proteins identified that despite their different cellular and molecular architectures, all phenotypes exhibited mitochondria- and stemness-related pathways under conditions of serum starvation, although the specific proteins involved were discrete to each phenotype. This suggests that common cellular programs in a disease can be mediated through variable biological networks that generates molecular heterogeneity. We further explored if these pathways are inter-related, co-regulated or just incidentally associated in response to an environment depleted of growth factors and mitogens. Irrespective of their phenotype, cell lines on serum-starvation displayed an increased amount of mitochondrial DNA, mitochondrial biogenesis and mitochondrial activity with a switch from glycolysis to oxidative phosphorylation fuelled by the fatty acid oxidation. Ultra-structural studies implicated this metabolic fluctuation was regulated by dynamic mitochondrial remodelling. This also led us to explore a possible therapeutic strategy of targeting mitochondrial function to restrict tumor regenerative potential and disease recurrence. Conclusively, these new avenues contribute to a more comprehensive understanding of ovarian cancer.
Insights
Ovarian cancer stem-like cells utilize distinct protein networks for self-renewal, driven by mitochondrial activity and metabolic shifts, even without serum. Targeting mitochondria may offer a therapeutic strategy against tumor recurrence.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Ex vivo stem cell maintenance relies on serum-free conditions to avoid mitogens.
- Ovarian cancer exhibits significant cellular and molecular heterogeneity, from epithelial to mesenchymal phenotypes.
- Understanding stem-like cell behavior in this heterogeneous environment is crucial for effective treatment.
Purpose of the Study:
- To investigate the proteomes of ovarian cancer stem-like cells across different phenotypes in serum-free media.
- To identify common and distinct molecular pathways related to stemness and mitochondria.
- To explore the metabolic adaptations and potential therapeutic targets in these cells.
Main Methods:
- Proteomic analysis using MaxQuant-based label-free quantification.
- Culturing high-grade serous ovarian cancer cell lines with varying phenotypes in serum-free media.
- Assessing mitochondrial DNA, biogenesis, activity, and ultrastructure.
- Investigating metabolic shifts from glycolysis to oxidative phosphorylation.
Main Results:
- All ovarian cancer phenotypes in serum-free conditions showed activated mitochondria- and stemness-related pathways.
- Specific proteins involved in these pathways were unique to each cell phenotype, indicating molecular heterogeneity.
- Serum starvation induced increased mitochondrial DNA, biogenesis, and activity, shifting metabolism towards fatty acid oxidation.
- Mitochondrial remodeling was implicated in regulating these metabolic fluctuations.
Conclusions:
- Common cellular programs in ovarian cancer can be executed through diverse biological networks, leading to molecular heterogeneity.
- Ovarian cancer stem-like cells adapt metabolically under serum starvation, enhancing mitochondrial function.
- Targeting mitochondrial function presents a potential therapeutic strategy to limit tumor regenerative potential and recurrence.
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