biologia - Studia

M. C. ALUPEI, R. M. MAXIM, M. BANCIU
HIF-1 is a transcription factor that induces further activation of various oncogenes
and/or mutation of tumor suppressor genes in tumor cells, which collectively
activate the proangiogenic/proinflammatory genes (encoding for vascular
endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)
cyclooxygenase (COX)-2) (Crowther et al., 2001; Sato, 2003). Moreover, in tumor
cells, hypoxia induces production of excessive reactive oxygen species (ROS),
which in turn modulates HIF-1 and proangiogenic protein synthesis.
The second angiogenic stage is called “inflammatory angiogenesis” due to the
involvement of infiltrated inflammatory cells overstimulated by microenvironmental
stress factors secreted by tumor cells (Crowther et al., 2001; Gupta et al., 1984; Albini
et al., 2005). In tumors, inflammatory cells such as macrophages, T cells, neutrophils,
eosinophils, monocytes, mast cells fully participate in the angiogenesis steps by
production of the majority of pro-angiogenic/pro-inflammatory factors that stimulate
recruitment, proliferation, migration and activation of the endothelial cells and
finally tumor blood vessel formation (Albini et al. 2005, Banciu, 2008; Naldini and
Carraro, 2005).
Consequently, oxidative stress and inflammation seems to be central forces
in tumor angiogenesis. Therefore, this review will briefly summarize the current
findings related to the involvement of oxidative stress and inflammation in tumor
angiogenesis.
Oxidative stress in tumor development
The oxidative stress is a state of the cell characterized by excessive
production of reactive oxygen species (ROS) (Dayem et al., 2010). In cellular
metabolism there is equilibrium between production of ROS and the antioxidant
mechanisms. Disturbance in the balance between oxidant and antioxidant
mechanisms in the favor of the generation of ROS will lead to the major damaging
effects on the important cellular components- proteins, nucleic acids and lipids
(Wienberg et al., 2010). In healthy cells, the physiological levels of ROS are
maintained by non-enzymatic and enzymatic antioxidant agents like glutathione,
thioredoxin, superoxide dismutase , catalase and peroxidases (Wang and Yi, 2008).
ROS have a major contribution in initiation, promotion and progression of
tumor cell phenotypes. ROS-mediated DNA damage is known to play an important
role in initiation of carcinogenesis due to their interaction with pyrimidines, purines
and chromatin proteins. As a result, tumor cells develop an increased rate in DNA
base modifications, genomic instability and modifications in gene expression
(Fruehauf and Meyskens, 2007). Oxidative stress induced by ROS is one of the
most important regulatory mechanisms involved in carcinogenesis through induction
of nuclear or mitochondrial DNA mutations, and oxidation of intracellular proteins
and lipids structures (Tandon et al., 2005).
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