Dataset Information

Chemoresistant Cancer Cell Lines Are Characterized by Migratory, Amino Acid Metabolism, Protein Catabolism and IFN1 Signalling Perturbations.

ABSTRACT: Chemoresistance remains the major barrier to effective ovarian cancer treatment. The molecular features and associated biological functions of this phenotype remain poorly understood. We developed carboplatin-resistant cell line models using OVCAR5 and CaOV3 cell lines with the aim of identifying chemoresistance-specific molecular features. Chemotaxis and CAM invasion assays revealed enhanced migratory and invasive potential in OVCAR5-resistant, compared to parental cell lines. Mass spectrometry analysis was used to analyse the metabolome and proteome of these cell lines, and was able to separate these populations based on their molecular features. It revealed signalling and metabolic perturbations in the chemoresistant cell lines. A comparison with the proteome of patient-derived primary ovarian cancer cells grown in culture showed a shared dysregulation of cytokine and type 1 interferon signalling, potentially revealing a common molecular feature of chemoresistance. A comprehensive analysis of a larger patient cohort, including advanced in vitro and in vivo models, promises to assist with better understanding the molecular mechanisms of chemoresistance and the associated enhancement of migration and invasion.

SUBMITTER: Acland M

PROVIDER: S-EPMC9179525 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Chemoresistant Cancer Cell Lines Are Characterized by Migratory, Amino Acid Metabolism, Protein Catabolism and IFN1 Signalling Perturbations.

Acland Mitchell M Lokman Noor A NA Young Clifford C Anderson Dovile D Condina Mark M Desire Chris C Noye Tannith M TM Wang Wanqi W Ricciardelli Carmela C Creek Darren J DJ Oehler Martin K MK Hoffmann Peter P Klingler-Hoffmann Manuela M

Cancers 20220602 11

Chemoresistance remains the major barrier to effective ovarian cancer treatment. The molecular features and associated biological functions of this phenotype remain poorly understood. We developed carboplatin-resistant cell line models using OVCAR5 and CaOV3 cell lines with the aim of identifying chemoresistance-specific molecular features. Chemotaxis and CAM invasion assays revealed enhanced migratory and invasive potential in OVCAR5-resistant, compared to parental cell lines. Mass spectrometry ...[more]

PMID: 35681748

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Project description:Uncertainty in risks posed by emerging stressors such as synthetic hormones impedes conservation efforts for threatened vertebrate populations. Synthetic hormones often induce sex-biased perturbations in exposed animals by disrupting gonad development and early life-history stage transitions, potentially diminishing per capita reproductive output of depleted populations and, in turn, being manifest as Allee effects. We use a spatially explicit biophysical model to evaluate how sex-biased perturbation in life-history traits of individuals (maternal investment in egg production and male-skewed sex allocation in offspring) modulates density feedback control of year-class strength and recovery trajectories of a long-lived, migratory fish-shovelnose sturgeon (Scaphirhynchus platorynchus)-under spatially and temporally dynamic synthetic androgen exposure and habitat conditions. Simulations show that reduced efficiency of maternal investment in gonad development prolonged maturation time, increased the probability of skipped spawning, and, in turn, shrunk spawner abundance, weakening year-class strength. However, positive density feedback disappeared (no Allee effect) once the exposure ceased. By contrast, responses to the demographic perturbation manifested as strong positive density feedback; an abrupt shift in year-class strength and spawner abundance followed after more than two decades owing to persistent negative population growth (a strong Allee effect), reaching an alternative state without any sign of recovery. When combined with the energetic perturbation, positive density feedback of the demographic perturbation was dampened as extended maturation time reduced the frequency of producing male-biased offspring, allowing the population to maintain positive growth rate (a weak Allee effect) and gradually recover. The emergent patterns in long-term population projections illustrate that sex-biased perturbation in life-history traits can interactively regulate the strength of density feedback in depleted populations such as Scaphirhynchus sturgeon to further diminish reproductive capacity and abundance, posing increasingly greater conservation challenges in chemically altered riverscapes.

Dataset Information

Chemoresistant Cancer Cell Lines Are Characterized by Migratory, Amino Acid Metabolism, Protein Catabolism and IFN1 Signalling Perturbations.

Publications

Chemoresistant Cancer Cell Lines Are Characterized by Migratory, Amino Acid Metabolism, Protein Catabolism and IFN1 Signalling Perturbations.

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