ANGIOGENSIS

Kelompok:
1.Rokh edy shofi
lotfyani
2.Eka sarofatul janah
Definition

Angiogenesisis the physiological process

through which newblood vesselsform from
pre-existing vessels

Angiogenesis is a normal and vital process in

growth and development, as well as in
wound healingand in the formation of
granulation tissue. However, it is also a
fundamental step in the transition oftumors
from a benign state to amalignantone,
leading to the use ofangiogenesis inhibitorsin
the treatment ofcancer.
Angiogenesis is a process controlled by certain chemicals produced in the
body. Some of these chemicals stimulate cells to repair damaged blood vessels
or form new ones. Other chemicals, called angiogenesis inhibitors, signal the
process to stop.

Angiogenesis Angiogenesis
Inhibitor Activator
Tissue inhibitor of
Vascullar endothelial growth
metallo proteinases factor (VEGF)
(TIMPs) aFGF
trombospondin bFGF
interukin -4, -12, -8. PDGF
TNF
Interferon (IFN , -,
Matrix protalloproteinases
- ), Plasminogen activators
Angiopocityn, TGF-
Endostatin Angiogenin
Interlukin-8
Troponin-1 Angioponictin-1
Platelet facor-4
 Type

Sprouting Angiogenesis Intussusceptive angiogenesis

First, the two opposing capillary

First, biological signals
walls establish a zone of contact.
known as angiogenic Second, the endothelial cell
growth factors activate junctions are reorganized and the
receptors present on vessel bilayer is perforated to
endothelial cells present in allow growth factors and cells to
pre-existing veins. penetrate into the lumen.
Second, the activated Third, a core is formed between
the two new vessels at the zone
endothelial cells begin to of contact that is filled with
release enzymes called pericytes and myofibroblasts.
proteases that degrade the These cells begin laying collagen
basement membrane in fibers into the core to provide an
order to allow endothelial extracellular matrix for growth of
cells to escape from the the vessel lumen.
The relationship between tumor and
angiogenesis
 While there are more than 100
distinct types of cancer (and
considerable heterogeneity within
each tumor type), there exists a
remarkable similarity in the
pathologic traits that collectively
drive tumor growth. Across mostif
not allmalignancies, sustained
angiogenesis is considered to be one
of these central hallmarks of cancer.
 Angiogenesis is a vital process in the progression of cancer
from small, localized neoplasms to larger, growing, and
potentially metastatic tumors. To grow beyond 1 to 2 mm in
diameter, a tumor needs an independent blood supply, which
is acquired by expressing growth factors that recruit new
vasculature from existing blood vessels. This process
continues even as the tumor matures. Thus, upregulation of
angiogenesis is a key step in sustained tumor growth and
may also be critical for tumor metastasis
 VEGF: the predominant
mediator of angiogenesis
VEGF (also known as VEGF-A, but commonly
referred to simply as VEGF) stands for vascular
endothelial growth factor. This protein plays an
important role in angiogenesis. As its name
suggests, VEGF stimulates vascular endothelial cell
growth, survival, and proliferation. As seen in
preclinical models, VEGF has been shown to
facilitate survival of existing vessels, contribute to
vascular abnormalities (eg, tortuousness and
hyperpermeability) that may impede effective
delivery of antitumor compounds, and stimulate
new vessel growth
 The VEGF Family Of
Proteins

VEGF is a member of a family of 6 structurally related

proteins (see table below) that regulate the growth and
differentiation of multiple components of the vascular
system, especially blood and lymph vessels. The angiogenic
effects of the VEGF family are thought to be primarily
mediated through the interaction of VEGF with VEGFR-2

There are 4 major isoforms of VEGFA (VEGF), each

coded for by a different portion of the VEGF gene.
These isoforms are VEGF121, VEGF165, VEGF189,
and VEGF206. Although these isoforms behave
identically in solution, they differ in their ability to
bind heparin and the extracellular matrix
RECEPTORS OF VEGF
GROWTH FACTORS

Three receptors have been identified that bind

different VEGF growth factors: VEGFR1 (FLT1),
VEGFR2 (Flk1/KDR), and VEGFR3 (FLT4) (initial
receptor names are given in parentheses)
These receptors belong to the superfamily of receptor
tyrosine kinases (RTK) and, based on their structural
peculiarities, they comprise a special class within it.
Like all RTK, the VEGF receptors are transmembrane
proteins with a single transmembrane domain
The extracellular region of VEGFR is formed by seven
immunoglobulin-like domains (IG I-VII), whereas the
intracellular part exhibits tyrosine kinase activity, and
the tyrosine kinase domain in these receptors is
separated to two fragments (TK-1 and TK-2) by an
inter-kinase insert All VEGFR receptors are highly
homologous .
THE
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