PMID- 30127847
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230928
IS  - 1754-1611 (Print)
IS  - 1754-1611 (Electronic)
IS  - 1754-1611 (Linking)
VI  - 12
DP  - 2018
TI  - A facile in vitro platform to study cancer cell dormancy under hypoxic 
      microenvironments using CoCl(2).
PG  - 12
LID - 10.1186/s13036-018-0106-7 [doi]
LID - 12
AB  - BACKGROUND: While hypoxia has been well-studied in various tumor 
      microenvironments, its role in cancer cell dormancy is poorly understood, in part 
      due to a lack of well-established in vitro and in vivo models. Hypoxic conditions 
      under conventional hypoxia chambers are relatively unstable and cannot be 
      maintained during characterization outside the chamber since normoxic response is 
      quickly established. To address this challenge, we report a robust in vitro 
      cancer dormancy model under a hypoxia-mimicking microenvironment using cobalt 
      chloride (CoCl(2)), a hypoxia-mimetic agent, which stabilizes hypoxia inducible 
      factor 1-alpha (HIF1alpha), a major regulator of hypoxia signaling. METHODS: We 
      compared cellular responses to CoCl(2) and true hypoxia (0.1% O(2)) in different 
      breast cancer cell lines (MCF-7 and MDA-MB-231) to investigate whether hypoxic 
      regulation of breast cancer dormancy could be mimicked by CoCl(2). To this end, 
      expression levels of hypoxia markers HIF1alpha and GLUT1 and proliferation marker 
      Ki67, cell growth, cell cycle distribution, and protein and gene expression were 
      evaluated under both CoCl(2) and true hypoxia. To further validate our platform, 
      the ovarian cancer cell line OVCAR-3 was also tested. RESULTS: Our results 
      demonstrate that CoCl(2) can mimic hypoxic regulation of cancer dormancy in MCF-7 
      and MDA-MB-231 breast cancer cell lines, recapitulating the differential 
      responses of these cell lines to true hypoxia in 2D and 3D. Moreover, distinct 
      gene expression profiles in MCF-7 and MDA-MB-231 cells under CoCl(2) treatment 
      suggest that key cell cycle components are differentially regulated by the same 
      hypoxic stress. In addition, the induction of dormancy in MCF-7 cells under 
      CoCl(2) treatment is HIF1alpha-dependent, as evidenced by the inability of 
      HIF1alpha-suppressed MCF-7 cells to exhibit dormant behavior upon CoCl(2) treatment. 
      Furthermore, CoCl(2) also induces and stably maintains dormancy in OVCAR-3 
      ovarian cancer cells. CONCLUSIONS: These results demonstrate that this 
      CoCl(2)-based model could provide a widely applicable in vitro platform for 
      understanding induction of cancer cell dormancy under hypoxic stress.
FAU - Lee, Hak Rae
AU  - Lee HR
AD  - Department of Chemical Engineering and Materials Science, University of 
      Minnesota, Minneapolis, MN 55455 USA. ISNI: 0000000419368657. GRID: grid.17635.36
FAU - Leslie, Faith
AU  - Leslie F
AD  - Department of Chemical Engineering and Materials Science, University of 
      Minnesota, Minneapolis, MN 55455 USA. ISNI: 0000000419368657. GRID: grid.17635.36
FAU - Azarin, Samira M
AU  - Azarin SM
AUID- ORCID: 0000-0003-0395-4988
AD  - Department of Chemical Engineering and Materials Science, University of 
      Minnesota, Minneapolis, MN 55455 USA. ISNI: 0000000419368657. GRID: grid.17635.36
LA  - eng
GR  - P30 CA077598/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20180803
PL  - England
TA  - J Biol Eng
JT  - Journal of biological engineering
JID - 101306640
PMC - PMC6091074
OTO - NOTNLM
OT  - Cancer dormancy
OT  - Cobalt chloride
OT  - Hypoxia
OT  - In vitro model
OT  - Tumor microenvironment
OT  - Tumor recurrence
COIS- Not applicable. Not applicable. The authors declare that they have no competing 
      interests. Springer Nature remains neutral with regard to jurisdictional claims 
      in published maps and institutional affiliations.
EDAT- 2018/08/22 06:00
MHDA- 2018/08/22 06:01
PMCR- 2018/08/03
CRDT- 2018/08/22 06:00
PHST- 2018/03/01 00:00 [received]
PHST- 2018/06/26 00:00 [accepted]
PHST- 2018/08/22 06:00 [entrez]
PHST- 2018/08/22 06:00 [pubmed]
PHST- 2018/08/22 06:01 [medline]
PHST- 2018/08/03 00:00 [pmc-release]
AID - 106 [pii]
AID - 10.1186/s13036-018-0106-7 [doi]
PST - epublish
SO  - J Biol Eng. 2018 Aug 3;12:12. doi: 10.1186/s13036-018-0106-7. eCollection 2018.