PMID- 28832662
OWN - NLM
STAT- MEDLINE
DCOM- 20171019
LR  - 20190115
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 8
DP  - 2017
TI  - Oxygen-dependent regulation of tumor growth and metastasis in human breast cancer 
      xenografts.
PG  - e0183254
LID - 10.1371/journal.pone.0183254 [doi]
LID - e0183254
AB  - BACKGROUND: Tumor hypoxia is relevant for tumor growth, metabolism, resistance to 
      chemotherapy and metastasis. We have previously shown that hyperoxia, using 
      hyperbaric oxygen treatment (HBOT), attenuates tumor growth and shifts the 
      phenotype from mesenchymal to epithelial (MET) in the DMBA-induced mammary tumor 
      model. This study describes the effect of HBOT on tumor growth, angiogenesis, 
      chemotherapy efficacy and metastasis in a triple negative MDA-MB-231 breast 
      cancer model, and evaluates tumor growth using a triple positive BT-474 breast 
      cancer model. MATERIALS AND METHODS: 5 x 105 cancer cells were injected s.c. in 
      the groin area of NOD/SCID female mice. The BT-474 group was supplied with 
      Progesterone and Estradiol pellets 2-days prior to tumor cell injection. Mice 
      were divided into controls (1 bar, pO2 = 0.2 bar) or HBOT (2.5 bar, pO2 = 2.5 
      bar, 90 min, every third day until termination of the experiments). Treatment 
      effects were determined by assessment of tumor growth, proliferation 
      (Ki67-staining), angiogenesis (CD31-staining), metastasis (immunostaining), EMT 
      markers (western blot), stromal components collagen type I, Itgb1 and FSP1 
      (immunostaining) and chemotherapeutic efficacy (5FU). RESULTS: HBOT significantly 
      suppressed tumor growth in both the triple positive and negative tumors, and both 
      MDA-MB-231 and BT-474 showed a decrease in proliferation after HBOT. No 
      differences were found in angiogenesis or 5FU efficacy between HBOT and controls. 
      Nevertheless, HBOT significantly reduced both numbers and total area of the 
      metastastatic lesions, as well as reduced expression of N-cadherin, Axl and 
      collagen type I measured in the MDA-MB-231 model. No change in stromal Itgb1 and 
      FSP1 was found in either tumor model. CONCLUSION: Despite the fact that behavior 
      and prognosis of the triple positive and negative subtypes of cancer are 
      different, the HBOT had a similar suppressive effect on tumor growth, indicating 
      that they share a common oxygen dependent anti-tumor mechanism. Furthermore, HBOT 
      significantly reduced the number and area of metastatic lesions in the triple 
      negative model as well as a significant reduction in the EMT markers N-cadherin, 
      Axl and density of collagen type I.
FAU - Yttersian Sletta, Kristine
AU  - Yttersian Sletta K
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
FAU - Tveitaras, Maria K
AU  - Tveitaras MK
AUID- ORCID: 0000-0003-3902-9225
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
AD  - Center for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway.
AD  - Matrix Biology, Haukeland University Hospital, Bergen, Norway.
FAU - Lu, Ning
AU  - Lu N
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
FAU - Engelsen, Agnete S T
AU  - Engelsen AST
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
AD  - Center for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway.
FAU - Reed, Rolf K
AU  - Reed RK
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
AD  - Center for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway.
FAU - Garmann-Johnsen, Annette
AU  - Garmann-Johnsen A
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
FAU - Stuhr, Linda
AU  - Stuhr L
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
AD  - Center for Cancer Biomarkers (CCBIO), University of Bergen, Bergen, Norway.
LA  - eng
PT  - Journal Article
DEP - 20170823
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/*pathology
MH  - Cell Line, Tumor
MH  - *Cell Proliferation
MH  - Epithelial-Mesenchymal Transition
MH  - Female
MH  - Humans
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - *Neoplasm Metastasis
MH  - Oxygen/*metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC5568407
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/08/24 06:00
MHDA- 2017/10/20 06:00
PMCR- 2017/08/23
CRDT- 2017/08/24 06:00
PHST- 2017/03/07 00:00 [received]
PHST- 2017/08/01 00:00 [accepted]
PHST- 2017/08/24 06:00 [entrez]
PHST- 2017/08/24 06:00 [pubmed]
PHST- 2017/10/20 06:00 [medline]
PHST- 2017/08/23 00:00 [pmc-release]
AID - PONE-D-17-09029 [pii]
AID - 10.1371/journal.pone.0183254 [doi]
PST - epublish
SO  - PLoS One. 2017 Aug 23;12(8):e0183254. doi: 10.1371/journal.pone.0183254. 
      eCollection 2017.