PMID- 34298602
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210729
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 14
DP  - 2021 Jul 6
TI  - 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.
LID - 10.3390/cancers13143388 [doi]
LID - 3388
AB  - 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 < 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.
FAU - Alharbi, Mona
AU  - Alharbi M
AD  - Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of 
      Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The 
      University of Queensland, Brisbane, QLD 4029, Australia.
AD  - Department of Biochemistry, College of Science, King Saud University, Riyadh 
      11451, Saudi Arabia.
FAU - Lai, Andrew
AU  - Lai A
AUID- ORCID: 0000-0002-4424-8767
AD  - Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of 
      Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The 
      University of Queensland, Brisbane, QLD 4029, Australia.
FAU - Sharma, Shayna
AU  - Sharma S
AD  - Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of 
      Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The 
      University of Queensland, Brisbane, QLD 4029, Australia.
FAU - Kalita-de Croft, Priyakshi
AU  - Kalita-de Croft P
AUID- ORCID: 0000-0001-8877-7655
AD  - Faculty of Medicine, University of Queensland Centre for Clinical Research, Royal 
      Brisbane and Women's Hospital, The University of Queensland, Herston, QLD 4029, 
      Australia.
FAU - Godbole, Nihar
AU  - Godbole N
AUID- ORCID: 0000-0002-6900-9551
AD  - Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of 
      Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The 
      University of Queensland, Brisbane, QLD 4029, Australia.
FAU - Campos, America
AU  - Campos A
AD  - Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of 
      Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The 
      University of Queensland, Brisbane, QLD 4029, Australia.
FAU - Guanzon, Dominic
AU  - Guanzon D
AD  - Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of 
      Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The 
      University of Queensland, Brisbane, QLD 4029, Australia.
FAU - Salas-Burgos, Alexis
AU  - Salas-Burgos A
AUID- ORCID: 0000-0002-6577-9970
AD  - Department of Pharmacology, Faculty of Biological Sciences, University of 
      Concepcion, Concepcion 4030000, Chile.
FAU - Carrion, Flavio
AU  - Carrion F
AUID- ORCID: 0000-0002-4086-6867
AD  - Departamento de Investigacion, Postgrado y Educacion Continua (DIPEC), Facultad 
      de Ciencias de la Salud, Universidad Pedro de Valdivia, Santiago 8320000, Chile.
FAU - Zuniga, Felipe A
AU  - Zuniga FA
AD  - Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, 
      University of Concepcion, Concepcion 4030000, Chile.
FAU - Perrin, Lewis
AU  - Perrin L
AD  - Mater Research Institute, University of Queensland, Translational Research 
      Institute, Woolloongabba, QLD 4102, Australia.
FAU - He, Yaowu
AU  - He Y
AUID- ORCID: 0000-0002-7828-263X
AD  - Mater Research Institute, University of Queensland, Translational Research 
      Institute, Woolloongabba, QLD 4102, Australia.
FAU - Pejovic, Tanja
AU  - Pejovic T
AD  - Departments of Obstetrics and Gynecology and Pathology, Oregon Health & Science 
      University, Portland, OR 97239, USA.
FAU - Winters, Carmen
AU  - Winters C
AD  - Departments of Obstetrics and Gynecology and Pathology, Oregon Health & Science 
      University, Portland, OR 97239, USA.
FAU - Morgan, Terry
AU  - Morgan T
AD  - Departments of Obstetrics and Gynecology and Pathology, Oregon Health & Science 
      University, Portland, OR 97239, USA.
FAU - Hooper, John D
AU  - Hooper JD
AUID- ORCID: 0000-0003-1054-8486
AD  - Mater Research Institute, University of Queensland, Translational Research 
      Institute, Woolloongabba, QLD 4102, Australia.
FAU - Rice, Gregory E
AU  - Rice GE
AD  - Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of 
      Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The 
      University of Queensland, Brisbane, QLD 4029, Australia.
AD  - Centro de Investigacion e Innovacion Biomedica, Universidad de los Andes, 
      Santiago 8320000, Chile.
FAU - Salomon, Carlos
AU  - Salomon C
AUID- ORCID: 0000-0003-4474-0046
AD  - Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of 
      Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, The 
      University of Queensland, Brisbane, QLD 4029, Australia.
AD  - Departamento de Investigacion, Postgrado y Educacion Continua (DIPEC), Facultad 
      de Ciencias de la Salud, Universidad Pedro de Valdivia, Santiago 8320000, Chile.
AD  - Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, 
      University of Concepcion, Concepcion 4030000, Chile.
LA  - eng
GR  - 1170809/Fondo Nacional de Desarrollo Cientifico y Tecnologico/
GR  - N/A/Lions Medical Research Foundation/
GR  - NA/National Health and Medical Research Council/
GR  - NA/Ovarian Cancer Research Foundation/
PT  - Journal Article
DEP - 20210706
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8305505
OTO - NOTNLM
OT  - exosomes
OT  - extracellular vesicles
OT  - hypoxia
OT  - ovarian cancer
COIS- The authors declare no conflict of interest.
EDAT- 2021/07/25 06:00
MHDA- 2021/07/25 06:01
PMCR- 2021/07/06
CRDT- 2021/07/24 01:00
PHST- 2021/06/14 00:00 [received]
PHST- 2021/06/27 00:00 [revised]
PHST- 2021/06/29 00:00 [accepted]
PHST- 2021/07/24 01:00 [entrez]
PHST- 2021/07/25 06:00 [pubmed]
PHST- 2021/07/25 06:01 [medline]
PHST- 2021/07/06 00:00 [pmc-release]
AID - cancers13143388 [pii]
AID - cancers-13-03388 [pii]
AID - 10.3390/cancers13143388 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Jul 6;13(14):3388. doi: 10.3390/cancers13143388.