Open Access

Biosci Bioeng Commun 2015; 1: 20-28

Bioscience and Bioengineering Communications

Journal Homepage: www.bioscibioeng.com

Invited Review

Tissue Factor and Breast Cancer

Amit Sarder1*, Md. Khadem Ali2 and Yuba Raj Pokharel1
1

Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, India;
2
Department of Biomedical Science, University of Newcastle, Australia.
Received: 6 Aug 2015; Received in Revised form: 20 Sep 2015; Accepted: 25 Sep 2015
Available online: 28 Sep 2015

Abstract
Tissue Factor (TF), a membrane bound glycoprotein, is the cellular initiator of the protease blood coagulation
cascade. TF is a component of tissue factor/factor VII (TF/FVII) complex which plays key roles in extrinsic
coagulation pathway. According to the traditional view of blood coagulation, although the initial phase of
coagulation is triggered by the extrinsic pathway, the amplification of the coagulation cascade is triggered by the
intrinsic pathway. Emerging experimental evidences show a broad range of biological functions of TF including
hemostasis, thrombosis, hypercoagulability etc. In addition to the role of TF as an initiator of coagulation cascade,
TF is also involved in many cancer-related processes like tumor growth, angiogenesis, metastasis etc. It is now
widely recognized that a strong correlation exists between TF expression and breast cancer and plasma TF
concentration has been found to be up-regulated in primary and recurrent breast cancer patients. TF-induced
thrombin can activate several members of the protease activated receptor (PAR) family. Expression of protease
activated receptor 1 (PAR1) is both required and sufficient to promote growth and invasion of breast carcinoma
cells. Like PAR1, protease activated receptor 2 (PAR2) has also been found to play a critical role in breast cancer
cell migration and invasion. Thus, TF plays a very crucial role in breast cancer progression. This review focuses on
the role of TF in breast cancer progression based on the evidences available. Better understanding the role of TF in
breast cancer will provide considerable clinical benefits associated with breast cancer treatment.

Keywords: Tissue factor, Breast cancer, Coagulation, Hemostasis, Thrombosis, Angiogenesis.

1. Introduction
Breast cancer is basically one kind of malignant tumor
initiated in the breast cells. The cancerous cells of the
malignant tumor can invade the surrounding tissues or
metastasize to distant parts of the body. Breast cancer
occurs almost exclusively in women though men can
also get it. It is estimated that an American woman has a
one in nine chance of developing breast cancer in her
lifetime. Familial breast cancer accounts for about 25%
of all the breast cancer cases in women under the age of
30 years. Again, genetic abnormalities of BRCA1 or
BRCA2 accounts for about 90-95% of familial breast
cancer while the remainder is caused by abnormalities
of other tumor suppressor genes or oncogenes like p53,
RAS (HRAS), hMLH1, hMSH2 etc. (Ross et al. 2003).
Corresponding
Sarder, Faculty
of of
Lifethe
Tissue
factor (TF) author:
which isAmit
a cellular
initiator
Sciencesblood
and Biotechnology,
South Asian
University,
protease
coagulation cascade
has been
foundNew
to be
Delhi, India. Email: [email protected]

expressed in a variety of solid tumors of epithelial

origin, particularly in carcinomas. There is a strong
correlation between expression of TF antigen in cellular
components of the stromal compartments and
progression to invasive cancer. Basically, the
recruitment and/or activation of TF-expressing stromal
cells is an early event in the progression to invasive
breast cancer. Thus, an association has been found
between the TF and the invasiveness of breast cancer
(Vrana et al. 1996).

2. Tissue Factor
2.1 Tissue Factor Biology
TF is a 47 kDa membrane bound glycoprotein
consisting of 263 amino acids present on the
subendothelial cells. Although the molecular weight for
the fully glycosylated protein is 47 kDa, the molecular
weight for the polypeptide chain of 263 amino acids is

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20

TF and breast cancer

predicted to be approximately 30kDa (van den Berg et
al 2012; Panes et al 2007). Tissue factor was first
purified in 1985. TF was first identified as a constituent
of tissue that when added to the plasma activates the
clotting cascade. Thats why it is named as tissue factor
(Broze et al. 1985; Macman and Taubman 2009).
TF is also called full-length TF (flTF), coagulation
factor III, thromboplastin or CD142 (Han et al 2014).
Full length TF contains a 219 amino acid extracellular
N-terminus and a 23 amino acid transmembrane domain
followed by an intracellular 21 amino acid C-terminus
(Chu 2011). The extracellular domain (residues 1-219)
representing the NH2 terminal is composed of two
fibronectin type III domains and it is involved in the
complex formation with activated factor VII (FVIIa).
The hydrophobic transmembrane domain (residues 220242) anchors TF to the membrane. The intracellular Cterminal domain (residues 243-263) is involved in
signal transduction. There are four potential N-linked
carbohydrate attachment sites (Asn
) in the
molecule among which three potential N-linked
carbohydrate attachment sites occur in the extracellular
domain (Butenas 2012; Spicer et al. 1987).
The gene of human TF is located on chromosome
1 p21-22 and spans approximately 12.4 kilobases. The
coding sequence of TF contains six exons. Exon one
corresponds to the translation initiation sites. Exons two
to exons five correspond to the sites for the translation
of the extracellular domain. Exon six constitutes
membrane spanning transmembrane domain and
cytoplasmic domain. The sequence of TF reveals a
distant homology to the cytokine receptor superfamily
and is also a member of the fibronectin type III family
(Butenas 2012; Bazan 1990).
2.2 Sources of Tissue Factor
The origin, nature and function of TFs are a
controversial issue. The best known function of TF is
clotting initiation (Panes et al. 2007). In addition to its
role in coagulation initiation, it also contributes to a
broad range of biological processes (Monroe and Key
2007). The function of TF includes thrombosis and
hemostasis (Mackman 2006), hypercoagulability
(Trousseau syndrome), tumor growth, angiogenesis,
metastasis (Rak et al 2006), smooth muscle cell
migration (Pyo et al. 2004), embryonic blood vessel
development (Carmeliet et al. 1996), induction of
proinflammatory response (Spek 2004) etc.
Blood-borne TF has been reported to be located on
blood cells, platelets, microparticles or circulates as a
soluble protein. It has been found that blood monocyte
is the major source of TF and activation of platelet
induces or enhances TF synthesis. Circulating platelets
contain enough TF to initiate clotting function. But,
resting monocytes express no functional TF because it

remains in an encrypted, inactive state. The interaction

of monocyte with activated platelets and neutrophils
induce the decryption of TF or the release of monocyte
derived microparticles carrying the active protein (Panes
et al. 2007; Butenas 2012).
There is a great debate regarding the localization
of TF. It has been found that TF circulates in plasma,
largely on microvesicles which can bind activated
platelets through mechanisms involving P-selectin
glycoprotein ligand 1 (PSGL-1) on the microvesicles
and P-selectin on the platelets. TF-bearing
microvesicles not only attach to activated platelets but
also fuse with them transferring both protein and lipid to
the platelet membrane and initiate coagulation (Del
Conde et al. 2005; Falati et al. 2003). But, another
report suggests both monocytes and polymorphonuclear
(PMN) leucocyte as source of TF that are transferred to
platelets (Rauch et al. 2000). Again, these findings
contrast with studies that show that TF is transferred
from platelets to monocytes (Scholz et al. 2002; Lsche
et al. 2004; Panes et al. 2007).
2.3 Tissue Factor and Coagulation Cascade Model
The coagulation system can be divided into three
pathways: the extrinsic pathway, the intrinsic pathway
and the common pathway (Mackman 2009). TF is a
very essential mediator of coagulation and also a potent
stimulator of extrinsic coagulation cascade. It also
enhances cell proliferation and migration (Poll 2008;
Han et al. 2014).
In the classic concept of coagulation, it is believed
that endothelial disruption leads to the exposure of flTF
to the bloodstream. Generally, TF is not exposed to the
circulating blood in a resting state. But, TF located at
the extravascular sites can become exposed to the
bloodstream due to the vascular injury or due to the
disruption of the endothelium. The exposed flTF can
then bind to its natural ligand human zymogen factor
VII (FVII) in the presence of calcium ions. FVII then
becomes activated serine protease FVII (FVIIa) (van
den Berg et al. 2012; Poll 2008; Spicer et al. 1987). The
activation of FVII bound to TF is considered as a key
early step in the TF pathway of blood coagulation (Rao
and Rapaport 1988). The flTF/FVIIa complex then
initiates coagulation activation by converting factor X
(FX) to activated factor X (FXa). FXa in turn allows
conversion of prothrombin to thrombin (factor IIa) (van
den Berg et al. 2012). This reaction occurs to a
significant extent after the thrombin-induced feedback
activation of factors V and VIII. FXa activates
prothrombin more than 105-fold more efficiently in
conjunction with activated factor V than in absence of
activated factor V. Thrombin subsequently activates
platelets and converts fibrinogen into fibrin. The
activation of platelets and conversion of fibrinogen into
fibrin are considered as two important and essential

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TF and breast cancer

components of a stable hemostatic plug (Poll 2008; van
den Berg et al. 2012). The presence of TF is prominent
in the perivascular cells which forms a hemostatic
barrier and limits the hemorrhage after vessel injury
(Liu et al. 2011). The TF: FVII/FVIIa complex is called
extrinsic pathway because exogenous TF is needed
for activation of clotting factors in plasma (Fig. 1)
(Mackman 2009).

prothrombinase complex (FVa/FXa) and activates

prothrombin to thrombin. Prothrombinase complex and
thrombin are referred to as the common pathway.
Thrombin in turn activates FXI which is an alternative
way to generate FIXa. It is assumed that thrombin
generated early in the clot formation activates FXI,
creating a feed-back loop which sustains coagulation.
Thrombin also activates factor XIII (FXIII), cleaves
fibrinogen and stimulates platelets. Platelets are
stimulated by thrombin via the cleavage of protease
activated receptors (PARs) (Fig. 2) (Mackman 2004;
Gailani and Renne 2007; Mackman 2009).

Fig 1. Extrinsic coagulation pathway.

Alternatively, coagulation can also be initiated through
the intrinsic pathway. In the early step of intrinsic
pathway, factor XII (FXII) becomes activated factor XII
(FXIIa) on a charged surface through the process of
contact activation. When blood comes into contact with
negatively charged surfaces, a series of proteolytic
reactions are initiated. The initiation of these reactions
results in the activation of FXII, prekallikrein (PK) and
factor XI (FXI). It also results in the cleavage of high
molecular weight kininogen (HK). These processes are
collectively called contact activation reactions (Gailani
and Renne 2007; Gailani and Renne 2007; Kaplan and
Silverberg 1987; Colman and Schmaier 1997).
Activation of FXII is followed by the activation event of
FXI in which FXI becomes activated factor XI (FXIa).
Activation of FXI is then followed by the activation
event of factor IX (FIX) to activated factor IX (FIXa).
The extrinsic and intrinsic pathways converge at the FX
activation level (Gailani and Renne 2007).
In fact, TF/FVIIa complex of the extrinsic pathway
initiates blood coagulation activating both FX and FIX.
The activated factor VIII (FVIIIa) then forms a complex
with FIXa and FVIIIa/FIXa complex then provides an
alternative route to generate FXa. The FXa then in
presence of activated factor V (FVa) participates in the

Fig 2. Intrinsic coagulation pathway and the common

pathway.
2.4 Tissue Factor in Hemostasis and Thrombosis
Hemostasis simply involves the mechanisms that
prevent loss of blood from the sites of vascular injury.
Thus, it maintains the integrity of the closed, highpressure circulatory system after vascular injury (Mller
et al. 2011; Furie and Furie 2008). Again, thrombosis
involves the mechanism of formation of blood clotting
leading to ischemia. TF has a major role in triggering
the hemostasis and thrombosis (Wu 2015). TF is
expressed in a tissue specific manner. TF/FVIIa
complex regulates hemostasis in a tissue specific
manner also and TF-dependent thrombin generation is
necessary for hemostasis in many vital organs
(Mackman 2009; Mackman 2005). In fact, TF is
essential for life because of its central role in

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TF and breast cancer

hemostasis. It provides a hemostatic envelope in order
to limit bleeding after vessel injury. Aberrant TF
expression within the vasculature can initiate lifethreatening thrombosis in diseases like sepsis,
atherosclerosis or even in cancer (Mackman 2004;
Mann et al. 2006).
Initiation of the coagulation cascade via exposure
of TF to blood and the formation of TF/FVIIa complex
are essential events for hemostasis and are initial
procuagulant signal in thrombosis (Wolberg and Mast
2012). Defects in the regulation of clot formation result
in either hemorrhage or thrombosis. Decreased levels of
fibrin lead to hemorrhage because of impaired
hemostasis. Again, increased levels of fibrin result in
intravascular thrombosis (Mackman 2005). According
to the traditional view of blood coagulation, the initial
phase of coagulation is triggered by the extrinsic
pathway whereas amplification of the coagulation
cascade is triggered by the intrinsic pathway (Mackman
et al. 2007).
Recent studies suggest that both FXII and FXI of
the intrinsic pathway are very important in thrombosis
and FXII-FXI contributes to a greater extent in
thrombus formation than to normal hemostasis. It is
assumed that FXI contribute to thrombin formation
when low amount of TF are present in the environment.
But, FXI is comparatively less important in the higher
TF environments (Mller et al. 2011). Human lacking
FXI generally show mild hemostatic defects. Thus,
intrinsic pathway can be viewed as important but not as
essential for human (Mackman 2009).

3. Tissue Factor and Tumor Progression

3.1 Tissue Factor and Angiogenesis
Angiogenesis can be defined as the development of new
blood vessel from the existing vasculature.
Angiogenesis and hemostasis are two of the most
consistent host responses associated with cancer.
Generally, TF maintains the vascular integrity upon
vessel injury by initiating the coagulation cascade.
Again, hypercoagulability contributes to the tumor
growth and metastasis by promoting angiogenesis.
Thus, angiogenesis and hemostasis are considered as
interrelated processes in cancer progression (Bluff et al.
2008). It is now accepted that the growth of tumor is
angiogenesis dependent because without proliferation of
blood vessels the growth of the tumor are limited to 12mm3 and can expand rapidly to 1-2 cm3 after
vascularization (Folkman 1990).
TF can contribute to angiogenesis either directly or
indirectly. In the direct regulation of angiogenesis,
angiogenesis is thought to be dependent on TF/FVIIa
function. The proteolytic activity of TF/FVIIa promotes
angiogenesis and tumor growth through a proangiogenic
mechanism and does not depend on hemostasis

(Hembrough et al. 2003). It has been found that

angiogenesis mediated by TF/FVIIa signaling is
regulated by protease activated receptor 2 (PAR-2)
signaling and PAR-2 signaling is sufficient for this
proangiogenic effect without the apparent role of
protease activated receptor 1 (PAR-1). It is obvious that
PAR-2 signaling is tightly controlled by the cytoplasmic
domain of TF. Thus, there is a direct contribution of TF
in angiogenesis. It is also assumed that the TF/FVIIa
might contribute to the angiogenesis simply by
stimulating cell division but the mitogenic capacity of
TF-FVIIa remains disputable (Uusitalo-Jarvinen et al.
2007; Belting et al. 2004; Bluff et al. 2008).
TF can contribute to the angiogenesis indirectly
via clotting dependent mechanisms. Clotting dependent
mechanism of tumor angiogenesis is mediated by the
TF-induced thrombin and the subsequent deposition of
cross-linked fibrin that provides a pro-angiogenic matrix
for blood vessel infiltration (Bluff et al. 2008). Again,
coagulation cascade and PAR-1 signaling can contribute
to angiogenesis by modulating endothelial cell function
in developing blood vessels. Thrombins actions on
endothelial cells rather than on platelets, mesenchymal
cells or fibrinogen can contribute to vascular
development and hemostasis (Griffin et al. 2001). Also,
there is evidence that tissue factor controls the
angiogenic properties of tumor cells by altering the
production of growth regulators of endothelium by a
mechanism distinct from TF activation of the
coagulation mechanism (Zhang et al. 1994).
3.2 Tissue Factor and Metastasis
Metastasis is the spread of malignant cells from a
primary tumor to distant sites and is the main cause of
death of cancer patients (Geiger and Peeper 2009).
Basically, metastasis is an enormous complex process
and by the process of metastasis cancer cells leave the
primary tumor and disseminate to anatomically distant
sites where they proliferate and form secondary tumor
foci (Hunter et al. 2008; Brooks et al. 2010). The first
evidence that thrombin can induce murine tumor cell
metastasis was given by Nierodzik and colleagues. They
reported that thrombin activation of tumor cells can
induce a metastatic phenotype by enhancing tumor cell
adhesion to pletelets, subendothelial matrix etc.
(Nierodzik et al. 1992; Nierodzik et al. 1991; Booden et
al. 2004). Subsequent studies have demonstrated that
TF is highly expressed in carcinoma cells and like
thrombin it can also contribute to metastasis (Mueller et
al. 1992; Booden et al. 2004; Mueller and Ruf 1998).
Tumor cell-associated TF and circulating hemostatic
factors contribute to tumor growth by increasing
metastatic potential. TF can increase metastatic
potential by supporting thrombin-mediated proteolysis.
It provides cancer cells a means of directing proteolytic
events leading to local thrombin generation and the

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TF and breast cancer

formation of tumor cell-associated microthrombi. TF
can also contribute to metastasis through TF
cytoplasmic domain mediated intracellular signaling
events, through activation of PARs mediated by the
TF/FVIIa/FXa or through a combination of these
processes (Palumbo et al. 2007).

4. Tissue Factor and Breast Cancer

TF is well known for its essential role in hemostasis.
Thus, it plays a great role in pathology associated with
hemostasis, triggering the coagulation system in many
thrombotic diseases. But, recent studies have also
implicated a variety of nonhemostatic role of TF like
cell signaling, inflammation, tumor growth and
metastasis etc. (Morrissey 2004; Wolberg and Mast
2012). Furthermore, studies have also revealed a
correlation between TF expression and breast cancer
and plasma TF concentration have been found to be upregulated in primary and recurrent breast cancer patients
(Ueno et al. 2000). There is novel experimental
evidence that ectopic expression of FVII is frequent in
cancer cells of different origin. Ectopic synthesis of
FVII was sufficient to drive the migration and invasion
of breast cancer cells (Koizume et al. 2006). TF
expression is very high in breast cancer tissue. Although
the detail mechanisms are not very clear, transcriptional
activation are thought to be a major mechanism of TF
overexpression. Constitutively high expression of F3
gene is regulated by many transcription factors.
Aberrant activation of these factors causes higher TF
expression in breast cancer (Koizume and Miyagi
2014).
PARs are G protein-coupled receptors (GPCRs)
which are uniquely activated by proteolysis. PARs are
predominantly expressed in vascular cells, immune
cells, epithelial cells etc. PAR family is comprised of
four members: Protease activated receptor 1 (PAR1),
Protease activated receptor 2 (PAR2), Protease activated
receptor 3 (PAR3) and Protease activated receptor 4
(PAR4) (Soh et al. 2010). PAR1, PAR3 and PAR4 can
be activated by TF-induced thrombin. On the other
hand, PAR2 can be activated by trypsin, tryptase as well
as FVIIa and Xa, but not by thrombin. PAR1 is
activated when thrombin cleaves its amino-terminal
extracellular domain or exodomain at specific site. This
cleavage unmasks a new N terminus which then serves
as a tethered ligand and effect transmembrane signaling
(Coughlin 2000).
PAR1 expression is found to be minimal or absent
in normal breast epithelial tissue. But, increased
expression of PAR1 has been correlated with invasion
of breast carcinoma cell (Booden et al .2004; Henrikson
et al. 1999). Expression of PAR1 is both required and
sufficient to promote growth and invasion of breast
carcinoma cells. The degree of invasiveness is directly

correlated with PAR1 expression levels. It has been

found that invasive breast cancer cell line expresses
very high levels of PAR1, PAR2 and PAR4. But,
minimally invasive cells have no PAR1 and low levels
of PAR2 and PAR4 (Boire et al. 2005; Cancino et al.
2007).
Activated PAR1 trafficking is severely altered in
metastatic breast carcinoma cells but not in
nonmetastatic or normal breast epithelial cells.
Alteration in trafficking of activated PAR1 causes
persistent signaling and contributes to breast carcinoma
cell invasion. The proteolytic activation of PAR1 by
thrombin is the cause of this continued signaling and the
signaling can also be continued even after the
withdrawal of thrombin (Booden et al. 2004; Even-Ram
et al. 1998). Proteolytic activation of PAR1 by thrombin
promotes cell invasion stimulating the induction of
persistent epidermal growth factor receptor (EGFR) and
ErbB2/HER2 and subsequently, a prolonged ERK1/2
signaling (Ohshiro et al. 2013). The mechanism by
which PAR1 persistently transactivates EGFR and
ErbB2 includes Gi/o signaling, metalloprotease activity
and release of heparin-binding epidermal growth factor
(HB-EGF) ligand. PAR1-stimulated EGFR and ErbB2
transactivation leads to prolonged extracellular signalregulated kinase 1 and signal-regulated kinase 2
signaling in breast carcinoma cell invasion. It is
important to note that ErbB2/HER2 is overexpressed in
approximately 20-30% of human invasive breast
cancers. ErbB2/Her2 overexpression is also correlated
with increased metastatic potential and increased patient
death. But, the mechanism by which activated PAR1
induces prolonged ERK1/2 signaling is not known
(Arora et al. 2008).
Like PAR1, PAR2 has also been found to play a
critical role in breast cancer cell migration and invasion.
The mechanism by which PAR2 promotes cancer cell
migration and invasion is poorly understood. But, there
is experimental evidence suggesting the role of PAR2 in
mediating FVIIa and FXa-induced signaling, migration
and invasion of breast cancer cells (Morris et al. 2006).
Again, there is evidence that thrombin-mediated PAR3
activation leads to extracellular signal-regulated kinase
(ERK) 1/2 phosphorylation and increased interleukin 8
production. But, PAR-3 from the human origin is
largely unexplored and its role in breast cancer is not
obvious (Ostrowska and Reiser 2008).
In addition to the flTF, identification of a form of
human TF generated by alternative splicing has been
reported. This alternatively spliced TF (asTF) is soluble
in nature and circulates in blood. When asTF is exposed
to phospholipids, it exhibits pro-coagulant activity. asTF
contains most of the extracellular domain of TF. But, it
lacks a transmembrane domain and terminates with a
unique peptide sequence (Bogdanov et al. 2003). Recent
experimental evidence suggests that asTF is abundantly

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TF and breast cancer

expressed in breast cancer cells and contribute to breast
cancer cell proliferation. asTF acts as a autocrine factor
and promotes breast cancer growth in a 1 integrindependent manner. Again, asTF can induce
angiogenesis independent of PAR2 activation, by acting
as an integrin ligand. This, flTF and asTF contribute in
cellular signaling via distinct mechanisms (Kocatrk et
al. 2013).
Progression of breast cancer is dependent on sex
hormone. Thus, proliferation of breast cancer is found to
be induced by progesterone metabolites. It has been
found that progesterone potently upregulate TF in breast
cancer cells. This progesterone-upregulated TF
contribute to breast cancer via TF-dependent pathway
(Kato et al. 2005; Henriquez et al. 2011).

5. Conclusion
Breast cancer is one of the leading cause of cancer death
in women worldwide. TF is highly expressed in breast
cancer cells. TF/FVII complex plays key roles in
extrinsic coagulation pathway. As FVII are profoundly
found in the cancer cells, TF-FVII complex can also be
formed in absence of injury. It is now well established
that TF/FVIIa complex can stimulate many malignant
phenotype
like
angiogenesis,
metastasis
etc.
Angiogenesis is thought to be dependent on TF/FVIIa
function. The proteolytic activity of TF/FVIIa promotes
angiogenesis and tumor growth through a proangiogenic
mechanism. Again, Tumor cell-associated TF and
circulating hemostatic factors contribute to tumor
growth by increasing metastatic potential. TF can also
contribute to metastasis through TF cytoplasmic domain
mediated intracellular signaling events, through
activation of PARs mediated by the TF/FVIIa/FXa or
through a combination of these processes. Thus,
TF/FVIIa complex has become an attractive target in
breast cancer treatment. The exact mechanism by which
TF is involved in breast cancer is not well understood.
Co-factors and other proteins involved in induction of
TF activity during angiogenesis and metastasis are
needed to be explored. Exploring transcription factors
which are involved to induce the function of TF could
give concrete idea to develop TF as a biomarker in
breast cancer. Again, it is necessary to explore the role
of TF to other genes which are involved in tumor
angiogenesis and metastasis. The development of
inhibitors which suppress the TF/FVIIa activity in
pathological angiogenesis but do not affect the
coagulation function can help in the specific drug design
essential for breast cancer treatment. Ectopic expression
of FVII also contributes to breast cancer progression.
So, inhibition of FVII expression can also represent a
valuable therapeutic mechanism is breast cancer
treatment. In addition to the flTF, asTF also plays a
major role in breast cancer cell proliferation. So,

understanding the detailed regulatory mechanism of

flTF as well as asTF will enable us in the development
of newer therapeutic strategies in the treatment of breast
cancer.

Acknowledgement
The authors would like to thank to Faculty of Life
Sciences and Biotechnology, South Asian University,
New Delhi, India to support this review work.

Conflict of interest
We declare that we have no conflict of interest

Abbreviations
TF: Tissue Factor, flTF: Full-length Tissue Factor,
FVIIa: Activated Factor VII, PSGL-1: P-Selectin
Glycoprotein Ligand 1, PMN: Polymorphonuclear,
FVII: Factor VII, FX: Factor X, FXa: Activated Factor
X, FXII: Factor XII, FXIIa: Activated Factor XII, FXI:
Factor XI, PK: Prekallikrein, HK: Kininogen, FXIa:
Activated Factor XI, FIX: Factor IX, FIXa: Activated
Factor IX, FVIIIa: Activated Factor VIII, FVa:
Activated Factor V, FXIII: Factor XIII, PAR: Protease
Activated Receptor,
PAR-2: Protease Activated
Receptor 2, PAR-1: Protease Activated Receptor 1,
GPCR: G protein-coupled receptor, PAR-3: Protease
Activated Receptor 3, PAR-4: Protease Activated
Receptor 4, EFGR: Epidermal Growth Factor Receptor,
HB-EGF: Heparin-binding Epidermal Growth Factor,
asTF: Alternatively Spliced Tissue Factor.

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How to cite this article: Sarder A, Ali MK and Pokharel YR (2015) Tissue factor and breast cancer. Biosci
Bioeng Commun; 1: 20-28.

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