Extracellular vesicle transmission of chemoresistance to ovarian cancer cells is associated with hypoxia-induced expression of glycolytic pathway proteins, and prediction of epithelial ovarian cancer disease recurrence

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dc.coverageDOI: 10.3390/cancers13143388
dc.creatorAlharbi, Mona
dc.creatorLai, Andrew
dc.creatorSharma, Shayna
dc.creatorKalita-De Croft, Priyakshi
dc.creatorGodbole, Nihar
dc.creatorCampos, America
dc.creatorGuanzon, Dominic
dc.creatorSalas-Burgos, Alexis
dc.creatorCarrion, Flavio
dc.creatorZuñiga, Felipe A.
dc.creatorPerrin, Lewis
dc.creatorHe, Yaowu
dc.creatorPejovic, Tanja
dc.creatorWinters, Carmen
dc.creatorMorgan, Terry
dc.creatorHooper, John D.
dc.creatorRice, Gregory E.
dc.creatorSalomon, Carlos
dc.date2021
dc.date.accessioned2025-11-18T19:52:09Z
dc.date.available2025-11-18T19:52:09Z
dc.description<p>Hypoxia is a key regulator of cancer progression and chemoresistance. Ambiguity remains about how cancer cells adapt to hypoxic microenvironments and transfer oncogenic factors to surrounding cells. In this study, we determined the effects of hypoxia on the bioactivity of sEVs in a panel of ovarian cancer (OvCar) cell lines. The data obtained demonstrate a varying degree of platinum resistance induced in OvCar cells when exposed to low oxygen tension (1% oxygen). Using quantitative mass spectrometry (Sequential Window Acquisition of All Theoretical Fragment Ion Mass Spectra, SWATH) and targeted multiple reaction monitoring (MRM), we identified a suite of proteins associated with glycolysis that change under hypoxic conditions in cells and sEVs. Interestingly, we identified a differential response to hypoxia in the OvCar cell lines and their secreted sEVs, highlighting the cells’ heterogeneity. Proteins are involved in metabolic reprogramming such as glycolysis, including putative hexokinase (HK), UDP-glucuronosyltransferase 1–6 (UD16), and 6-phosphogluconolactonase (6 PGL), and their presence correlates with the induction of platinum resistance. Furthermore, when normoxic cells were exposed to sEVs from hypoxic cells, platinum-resistance increased significantly (p &lt; 0.05). Altered chemoresistance was associated with changes in glycolysis and fatty acid synthesis. Finally, sEVs isolated from a clinical cohort (n = 31) were also found to be enriched in glycolysis-pathway proteins, especially in patients with recurrent disease. These data support the hypothesis that hypoxia induces changes in sEVs composition and bioactivity that confers carboplatin resistance on target cells. Furthermore, we propose that the expression of sEV-associated glycolysis-pathway proteins is predictive of ovarian cancer recurrence and is of clinical utility in disease management.</p>eng
dc.identifierhttps://investigadores.uandes.cl/en/publications/366610f6-799b-4f9b-a8b3-476f9e59b5bc
dc.identifier.urihttps://repositorio.uandes.cl/handle/uandes/57563
dc.languageeng
dc.rightsinfo:eu-repo/semantics/openAccess
dc.sourcevol.13 (2021) date: 2021-07-02 nr.14
dc.subjectExosomes
dc.subjectExtracellular vesicles
dc.subjectHypoxia
dc.subjectOvarian cancer
dc.subjectSDG 3 - Good Health and Well-being
dc.titleExtracellular vesicle transmission of chemoresistance to ovarian cancer cells is associated with hypoxia-induced expression of glycolytic pathway proteins, and prediction of epithelial ovarian cancer disease recurrenceeng
dc.typeArticleeng
dc.typeArtículospa
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