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

Mitchell Acland; Noor A Lokman; Clifford Young; Dovile Anderson; Mark Condina; Chris Desire; Tannith M Noye; Wanqi Wang; Carmela Ricciardelli; Darren J Creek; Martin K Oehler; Peter Hoffmann; Manuela Klingler-Hoffmann

doi:10.3390/cancers14112763

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

Cancers (Basel). 2022 Jun 2;14(11):2763. doi: 10.3390/cancers14112763.

Authors

Affiliations

¹ Clinical & Health Sciences, University of South Australia, Adelaide, SA 5095, Australia.
² Adelaide Proteomics Centre, School of Biological Sciences, The University of Adelaide, Adelaide, SA 5000, Australia.
³ Discipline of Obstetrics and Gynaecology, Adelaide Medical School, Robinson Research Institute, The University of Adelaide, Adelaide, SA 5005, Australia.
⁴ Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
⁵ Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA 5005, Australia.

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.

Keywords: cancer cell lines; chemoresistance; metabolomics; ovarian cancer; proteomics.

Grants and funding

P.H. gratefully acknowledges the support of the National Collaborative Research Infrastructure Strategy (NCRIS) node for Tissue Imaging Mass Spectrometry.