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Table 2
Direct and indirect effects of Epo on tumor growth and angiogenesis
Effect
Reference
Direct
Increased expression of Ki67 proliferation antigen
(
18
)
Enhanced microvessel density
(
18
)
Decreased tumor hypoxia
(
18
)
Increased mobilization of EPC
(
16
)
Indirect
Increased release of VEGF and PlGF by tumor cells (
14
)
EPC
endothelial precursor cells;
VEGF
vascular endothelial growth factor;
PlGF
placen-
tal growth factor
carcinoma cells stimulated tumor neovascularization and growth (
18
).
Epo administration to patients with hematological malignancies
induced bone marrow angiogenesis and further malignant trans-
formation in plasma cell leukemia and acute monoblastic leukemia,
respectively (
19-21
).
The administration of anti-Epo-antibody, soluble EpoR, or an
inhibitor of JAK2 resulted in a delay in tumor growth with 45%
reduction in maximal tumor depth in a tumor Z chambers model
with rat mammary adenocarcinoma cells (
22
). On the contrary, the
injection of an antibody anti-Epo or the soluble form of EpoR into
in malignant tumors of the female reproductive organs reduces
capillaries and causes tumor destruction (
23
). Moreover, blockade
of Epo signalling on xenografts of uterine and ovarian cancer leads
to the destruction of tumors in nude mice.
The mechanism of tumor growth in the context of Epo is not
completely clarified, and it is not still clear whether there is a direct
effect of Epo in tumor cells as opposed to exogenous effect on
angiogenesis (Table
2
). It is also possible that the effect of Epo is
multifactorial depending on the type of tumor and level or func-
tionality of EpoR expression in tumor cells as well as other vari-
ables such as hypoxic stress, degree of anemia, chemotherapy,
radiotherapy, or surgical intervention.
The chick embryo chorioallantoic membrane (CAM) is an
extraembryonic membrane which serves as a gas exchange surface
and it function is supported by a dense capillary network (
24
).
Because of its extensive vascularization and easy accessibility, the
CAM has been broadly used to study the morphofunctional aspects
of the angiogenesis process in vivo and to investigate the efficacy
and mechanisms of action of pro-angiogenic and anti-angiogenic
natural and synthetic molecules.
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