Biology Reference
In-Depth Information
before and/or after treatment, their role and function have not been clearly
assessed (
Ahn et al., 2010; Mancuso et al., 2001; Morita et al., 2011; Nowak
et al., 2010
). The main hypothesis for tumor biology is based on the assump-
tion that EPCs are mobilized from BM in response to paracrine signals gen-
erated by ischemic tissue and tumor cells including G-CSF and VEGF
(
Dome et al., 2006; Furstenberger et al., 2006; Morita et al., 2011;
Nowak et al., 2010; Spring et al., 2005
), which play a critical role in mobi-
lization of EPC to ischemic tissues and tumors. Hypoxia in tumors and
ischemic tissues mediates EPC recruitment by activation of HIF-1a which
leads to increased synthesis of a potent angiogenic factor VEGF (
Wels et al.,
2008
). Also, growing tumors secrete a number of other factors such as FGF,
or a variety of CC chemokines such as CCL2 and CCL5, which amply con-
tribute to EPC mobilization (
Spring et al., 2005
).
The concept of EPCs taking a role in neoangiogenesis has been mostly
accepted as an essential mechanism leading to neoangiogenesis and tumor
growth promotion (
Lyden et al., 2001; Nolan et al., 2007
). A study with
tagged BM estimated that the BM-EPC could constitute as much as half
of all ECs in tumor neovessels (
Garcia-Barros et al., 2003
). These amounts
seem to be far too high, as other studies have advocated amounts of 2-12%
(
Peters et al., 2005
), or even no contribution at all (
De Palma et al., 2003;
Purhonen et al., 2008
). Various studies have also shown that the cells
detected in the commonly used EPC assays are in fact white blood cells
(
Case et al., 2007; Kim et al., 2009; Rehman et al., 2003; Rohde et al.,
2006
). There is strong evidence that CEPCs are involved in the develop-
ment and the severity of disease in lung cancer patients (
Nowak et al.,
2010
). Additionally, there is evidence that EPCs derived from CD34
þ
PBMCs are mobilized mainly into tumor areas after being injected through
the tail vein in mice (
Ahn et al., 2010
). Considering all these data, it becomes
obvious that the main problem is the use of different protocols for identify-
ing EPC. Further, the transfer of evidence from mouse to human and the
other way round is used, although these conclusions cannot be made. In
conclusion, it is not sure if CEPCs or CACs are involved in tumor devel-
opment growth and angiogenesis, as long there is no common ground for
identifying “EPC.”
3.2.7 Inflammatory diseases
Rheumatoid arthritis (RA) and systemic sclerosis (SSc) are the inflammatory
diseases that have been studied the most in relation to EPC cell counts and cell
function. In 2005, a study published by Grisar et al. observed the changes of
Search WWH ::
Custom Search