PMID- 17882938
OWN - NLM
STAT- MEDLINE
DCOM- 20071009
LR  - 20070921
IS  - 1505-1773 (Print)
IS  - 1505-1773 (Linking)
VI  - 10
IP  - 2
DP  - 2007
TI  - Possible implications of redox-sensitive tumour cell transformation; lessons from 
      cell culture studies.
PG  - 123-6
AB  - It is generally accepted that chronic inflammatory disease, either local or 
      generalized, is associated with higher incidence of cancer. Since inflammation is 
      often accompanied by oxidative stress the latter was indicated as the foundation 
      for progressive mutations leading to tumor development (proliferation, invasion, 
      metastasis). Even though, it is very hard to demonstrate by in vitro studies the 
      causal relationship between oxidative stress and cell transformations. From our 
      studies it is clear that cells are more likely to stop divisions and they commit 
      suicide by apoptosis. During last decade, a novel view on the origin of cancer 
      emerged. The so called cancer stem cells (CSC) were found that form the 
      side-population of stem cells (SC) and they are believed to initiate cancer. Are 
      the SC ancestors for CSC? Do SC transform into CSC? These and other questions 
      remain unanswered. We hypothesize that SC might undergo transformation into CSC 
      during prolonged oxidative stress. We claim that several changes in cell 
      biochemistry has to occur to start the molecular modifications leading to 
      neoplasma. These include either hypoxia-promoted apoptosis signal inducing kinase 
      1 (ASK-1), hypoxia inducing factor 1 alpha (HIF-1alpha) and glycolysis, or 
      normoxia-promoted activating protein-1 (AP-1) or hyperoxia-induced nuclear factor 
      kappa B (NF-kappaB). Next, harsh microenvironment and heterogenous extracellular 
      matrix (ECM) induced by oxidative stress accelerate the selection of clones of 
      cells resistant to apoptogenic signal. HIF-1alpha, protein crucial for 
      transcriptional activation of protooncogene met leads to the overexpression of 
      c-Met receptor that in turn sensitizes cells to hepatocyte growth factor/scatter 
      factor (HGF/SF) mitogen. Finally, both impaired function of mitochondria and 
      hypoxia elevate fibrin protein level and amplify hemostasis as disseminated 
      intracapillary coagulation (DIC). In any case, it is very interesting and remains 
      to be answered whether imbalance in prooxidant-antioxidant homeostasis has causal 
      relationship with transformation of SC to CSC.
FAU - Orzechowski, A
AU  - Orzechowski A
AD  - Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw 
      Agricultural University, Nowoursynowska 159, 02-776 Warsaw, Poland. 
      arkadiusz-orzechowski@sggw.pl
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Pol J Vet Sci
JT  - Polish journal of veterinary sciences
JID - 101125473
SB  - IM
MH  - Animals
MH  - Cell Hypoxia
MH  - Cell Transformation, Neoplastic/*pathology
MH  - Cells, Cultured
MH  - Stem Cells/*pathology
RF  - 20
EDAT- 2007/09/22 09:00
MHDA- 2007/10/10 09:00
CRDT- 2007/09/22 09:00
PHST- 2007/09/22 09:00 [pubmed]
PHST- 2007/10/10 09:00 [medline]
PHST- 2007/09/22 09:00 [entrez]
PST - ppublish
SO  - Pol J Vet Sci. 2007;10(2):123-6.