Circulating endothelial cells (CEC) and endothelial progenitor cells (EPC) are markers of vascular damage and neovascularization, respectively. CEC detach from vessel walls during endothelial damage and reflect loss of vascular integrity, while EPC originate from bone marrow and contribute to new blood vessel formation. Both cell types are elevated in cancers and other diseases involving vascular dysfunction. CEC are mature endothelial cells in the blood indicating severe damage, whereas EPC are immature progenitor cells that promote neovascularization through differentiation into new endothelial cells. Together, CEC and EPC provide insights into vascular pathology and angiogenesis.

1. Circulating Endothelial Cells and
Endothelial Progenitor Cells
Hema T
MSc Biochemistry
Bharathiar University

2. Tumor Markers
• A tumor marker is anything present in or produced by cancer cells or
other cells of the body in response to cancer or certain benign
(noncancerous) conditions
• provides information about a cancer, such as how aggressive it is,
whether it can be treated with a targeted therapy, or whether it is
responding to treatment.
• They are proteins or other substances that are made by both normal
and cancer cells but at higher amounts by cancer cells.
• These can be found in the blood, urine, stool, tumors, or other tissues
or bodily fluids of some patients with cancer.

3. How are tumor markers used in cancer care?
• There are two main types of tumor markers that have different uses
in cancer care:
• circulating tumor markers and
• tumor tissue markers.

4. Circulating tumor markers
• Circulating tumor markers can be found in the blood, urine, stool, or
other bodily fluids of some patients with cancer.
• Circulating tumor markers are used to:
• estimate prognosis
• detect cancer that remains after treatment (residual disease) or that has
returned after treatment
• assess the response to treatment
• monitor whether a cancer has become resistant to treatment

5. • Tumor markers may also be measured periodically during cancer
therapy.
• For example, a decrease in the level of a circulating tumor marker
may indicate that the cancer is responding to treatment,
• whereas an increasing or unchanged level may indicate that the
cancer is not responding.
• Circulating tumor markers may also be measured after treatment has
ended to check for recurrence (the return of cancer).

6. Commonly used circulating tumor markers
• calcitonin (measured in blood) -to assess treatment response, screen
for recurrence, and estimate prognosis in medullary thyroid cancer;
• CA-125 (measured in blood) -to monitor how well cancer treatments
are working and if cancer has come back in ovarian cancer; and
• beta-2-microglobulin (measured in blood, urine, or cerebrospinal
fluid) -to estimate prognosis and follow response to treatment for
multiple myeloma, chronic lymphocytic leukemia, and some
lymphomas.

7. Circulating endothelial cells
• The presence of circulating endothelial cells (CEC) has recently been
recognized as a useful marker of vascular damage.
• Usually absent in the blood of healthy individuals, CEC counts are
elevated in diseases hallmarked by the presence of vascular insult,
such as sickle cell anemia, acute myocardial infarction,
Cytomegalovirus (CMV) infection, endotoxemia, and neoplastic
processes.
• CEC are cells driven from the intima after vascular insult, and are thus
the consequence—rather than the initiator—of a particular pathology

8. Fluorescence microscopy of a large CEC rosetted by
immunobeads.

9. Origin and pathophysiology of CEC
• The endothelium can be viewed as a membrane-like layer lining the
circulatory system, its primary function being the maintenance of
vessel wall permeability and integrity.
• Proliferation seems to occur mainly at sites of vasculature branching
and turbulent flow.
• EC are thought to have “sloughed off” vessel walls, indicating severe
endothelial damage
• CEC have been shown to correlate with various endothelial
dysfunction and inflammatory markers

11. • CEC detachment from the endothelium involves multiple factors, such
as
• mechanical injury,
• alteration of endothelial cellular adhesion molecules (such as integrin αVβ3),
• defective binding to anchoring matrix proteins (such as fibronectin, laminin,
or type IV collagen), and
• cellular apoptosis with decreased survival of cytoskeletal proteins.
• The net effect is a reduced interaction between the EC and basement
membrane proteins, with subsequent cellular detachment.

12. • Depending on the disease process, the vessel origin of CEC can vary
significantly.
• CEC in diseases such as cancer, thalassemia, and sickle cell disease are
of from microvascular (CD36) origin.
• EC in acute coronary syndrome and systemic lupus erythematosus
(SLE) patients were from the macrovasculature.
• By analyzing the phenotypic expression of CEC, important knowledge
on the severity and pathogenesis of vascular diseases can be obtained
in a relatively noninvasive manner.

13. CEC in cancer
• Elevated numbers of CEC have been variously described in
• lymphoma,
• melanoma, and
• glioma patients,
• as well as in breast, colonic, gastric, esophageal, renal cell, ovarian,
cervical, carcinoid, testicular, prostate, and head and neck cancer
patients, reflecting the perturbation of vascular endothelium in
cancer disease.

14. Endothelial Progenitor Cells
• A related circulating cell population are endothelial progenitor cells
(EPC), which originate from the bone marrow, rather than from vessel
walls.
• Seen in small numbers in healthy individuals, their numbers tend to
increase following vascular injury.
• So far, experiments have established the ability of EPC to form
colonies in vitro, suggesting a role in both angiogenesis and in the
maintenance of existing vessel walls.
• Recent evidence has suggested the involvement of EPC in tumor
vasculogenesis.

15. Origin and pathophysiology of EPC
• EPC are potentially crucial for neovascularization and may be
recruited from the bone marrow after tissue ischemia, vascular insult,
or tumor growth.
• They possess the ability to migrate, colonize, proliferate, and,
ultimately, differentiate into endothelial lineage cells.
• These cells have yet to acquire mature EC characteristics while
appearing to contribute to vascular homeostasis.

17. • EPC have been isolated previously from human umbilical cord blood,
adult bone marrow, human fetal liver cells, and cytokine-mobilized
peripheral blood,
• an increase in circulating EPC follows in vivo administration of the
angiogenic growth factor VEGF(Vascular Endothelial Growth Factor).
• EPC recruitment and mobilization have been positively correlated
with increased levels of angiogenic growth factors such as VEGF.
• VEGF induces the proliferation, differentiation, and chemotaxis of
EPC, and is essential for hematopoiesis, angiogenesis, and, ultimately,
survival.

18. Cancer, Neovascularization, and EPC
• Blood vessels are essentially composed of EC that align and
interconnect, forming tubes for directing and maintaining blood flow.
• The traditionally accepted view is that neovascularization in adult life
occurs by a process known as angiogenesis, whereby new capillaries
sprout from existing vasculature as vessel wall-associated EC
proliferate and migrate.
• New research has suggested an alternative means by which vessels
are formed, namely, by postnatal vasculogenesis or by differentiation
of primitive/progenitor EC into mature EC .
• These cells originate from the bone marrow cell population, with
subsequent mobilization and homing to sites of vascular growth and
repair

19. Differences Between CEC and EPC
Plasma Marker CEC EPC
Origin Mature endothelium
Bone marrow, cord blood,
mobilized MC
Morphology
Mature cells 20–50 µM in
diameter
Immature cells <20 µM in
diameter
Phenotype CD133 -ve/CD146 +ve
CD133 +ve/CD34 +ve/KDR +
CD146 -ve
High proliferative potential No Yes
Pathophysiology Reflective of damage Neovascularization
Laboratorymethods
Immunomagnetic isolation,
FACS
FACS, culture assays

20. Summary
• CEC elevation in the blood of patients is becoming established as a
useful marker for severe vascular dysfunction.
• The presence of CEC in significant numbers denotes a high degree of
vascular damage and, in this respect, is more useful as a clinical
marker
• CEC reflect loss of vascular integrity to some degree (e.g., in the case
of necrotic tumors or in postchemotherapy tumors).
• EPC have a potentially significant role to play in the evaluation of
tumor angiogenesis and growth

21. THANK YOU