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Review Article
Hepatobiliary & Pancreatic Diseases International
The diversity between pancreatic head and
body/tail cancers: clinical parameters and
in vitro models
Qi Ling, Xiao Xu, Shu-Sen Zheng and Holger Kalthoff
Hangzhou, China
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC)
can be divided into head, body and tail cancers according to the
anatomy. Distinctions in tissue composition, vascularization
and innervations have been clearly identified between the head
and body/tail of the pancreas both in embryological development
and in histopathology. To understand the postulated genotype
difference, we present comprehensive information on two PDAC
cell lines as typical representatives originating from pancreatic
head and body/tail cancers, respectively.
DATA SOURCE: In the present review, we compare the difference
between pancreatic head and body/tail cancers regarding clinical
parameters and introducing an in vitro model.
RESULTS: Increasing evidence has shown that tumors at
different locations (head vs body/tail) display different clinical
presentation (e.g. incidence, symptom), treatment efficiency (e.g.
surgery, chemotherapy) and thus patient prognosis. However,
the genetic or molecular diversity (e.g. mutations, microRNA)
between the two subtypes of PDAC has not been elucidated
so far. They present different chemo- and/or radio-resistance,
extracellular matrix adhesion and invasiveness, as well as
genetic profiles.
Author Affiliations: Division of Hepatobiliary and Pancreatic Surgery,
Department of Surgery, First Affiliated Hospital, Zhejiang University School
of Medicine; Key Lab of Combined Multi-Organ Transplantation, Ministry
of Public Health, Hangzhou 310003, China (Ling Q, Xu X and Zheng SS);
Institute for Experimental Cancer Research, Comprehensive Cancer Center
North, UK S-H, Campus Kiel, 24105, Germany (Ling Q and Kalthoff H)
Corresponding Author: Prof. Holger Kalthoff, Institute for Experimental
Cancer Research, Comprehensive Cancer Center North, UK S-H, Campus
Kiel, 24105, Germany (Tel: 49-431-5971938; Fax: 49-431-5971939; Email:
[email protected]); Prof. Shu-Sen Zheng, Division of Hepatobiliary
and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital,
Zhejiang University School of Medicine; Key Lab of Combined Multi-Organ
Transplantation, Ministry of Public Health, Hangzhou 310003, China (Tel/Fax:
86-571-87236567; Email: [email protected])
© 2013, Hepatobiliary Pancreat Dis Int. All rights reserved.
doi: 10.1016/S1499-3872(13)60076-4
CONCLUSION: Genetic and tumor biological diversity exists in
PDAC according to the tumor localization.
(Hepatobiliary Pancreat Dis Int 2013;12:480-487)
KEY WORDS: pancreatic ductal adenocarcinoma;
tumor location;
cell lines;
diversity
Introduction
P
ancreatic ductal adenocarcinoma (PDAC) is one
of the most lethal human cancers. It has a high
metastatic potential and the majority of diseases
present themselves at a very late stage. PDAC can be
divided into head and body/tail cancers according to
the anatomy. Pancreatic development begins with the
formation of a ventral and a dorsal bud, which becomes
the ventral head (lower head and uncinate process) and
dorsal pancreas (upper head, body and tail), respectively.
This difference in ontogeny leads to significant
differences in cell composition, blood supply, lymphatic
and venous backflow, and innervations between the head
and body/tail of the pancreas. For instance, the number
of Langerhans Islets is greater in the body and tail.
Insulin-positive endocrine cells are highly refractory to
malignant transformation under normal conditions, but
could serve as a cell-of-origin of PDAC under oncogenic
activation in combination with pancreatic injury.[1]
In addition, fatty tissue infiltration is usually most
prominent in the anterior aspect of the pancreas head
and may stimulate pancreatic neoplasm.[2, 3] Branch duct
intraductal papillary mucinous neoplasms are typically
arising in the head of the pancreas while mucinous
cystic neoplasms are common in the body or tail.[4] In
this sense, the head and body/tail of the pancreas may
have different malignant potential.
In pancreatic serous cystic neoplasms and
intraductal papillary mucinous neoplasms, tumor
480 • Hepatobiliary Pancreat Dis Int，Vol 12，No 5 • October 15，2013 • www.hbpdint.com
Diversity between pancreatic head and body/tail cancers
location in the head of the pancreas was independently
associated with local invasiveness and recurrence,[5, 6]
while in pancreatic neuroendocrine tumors, tumors
located at the body/tail of the pancreas were more likely
to be associated with shorter progression-free survival.[7]
In colon cancer, a number of studies have demonstrated
that right- and left-sided tumors exhibit different
genetic, biological and demographical characteristics
and risk factors, suggesting that the carcinogenesis
and tumor progression of colon cancer may differ with
tumor localization.[8-10] These findings support the
hypothesis of different mechanisms in carcinogenesis
of tumors at different locations and confirm the
importance of subsite division. Although increasing
evidence has shown differences in clinical presentation
between pancreatic head and body/tail cancers,[11-15] the
genetic or molecular diversity between the two subtypes
of PDAC has not been elucidated so far.
In the present review, we compare the clinical data
between pancreatic head and body/tail cancers. In
particular, to assess the potential phenotype and genotype
difference, we provide comprehensive information on
two frequently used PDAC cell lines that originate from
pancreatic head and body/tail cancers, respectively.
Comparison of clinical and diagnostic parameters
between pancreatic head and body/tail cancers
Incidence
Data from Surveillance, Epidemiology, and End Results
(SEER) registries of the United States (1973-2002)
have shown that about 77.5% (34 072/43 946) of
PDACs originate at the head of the pancreas, on which
consequently most discussion on pancreatic cancer
has been focused.[11] The overall annual incidence of
pancreatic head cancer is 5.6 per 100 000, compared
with 1.6 of pancreatic body/tail cancer.[11] Data from
National Pancreatic Cancer Registry of Japan (1981-2002,
n=9290)[13] and Eindhoven Cancer Registry of
Netherland (1995-2000, n=1128)[14] also demonstrated
much higher incidences of pancreatic head cancer
(62.3% and 56.5%, respectively) than body/tail cancer
(17.5% and 12.7%, respectively). For resectable tumors
(Stage I: T1N0M0 and T2N0M0), about 69.8% (6676/9559)
are located in the head of the pancreas as shown by the
United States National Cancer Data Base, 1995-2004.[12]
Early diagnosis
Symptoms often do not appear until the disease
is in an advanced stage, thus making early detection
difficult. Notably, a patient's symptoms will vary
depending on the location of the tumor within the
pancreas. Both pancreatic head and body/tail cancers
can cause non-specific symptoms, such as abdominal
pain, nausea, loss of appetite and weight loss. However,
only tumor blocking the bile ducts, which pass through
the head of the pancreas, can cause jaundice. A study
from China investigated the clinicopathological
characteristics between pancreatic head cancer (n=541)
and body/tail cancer (n=106) from 1980 to 2003. It
was found that patients primarily diagnosed with
pancreatic body/tail cancer were associated with much
less jaundice but more pain, higher serum albumin
level, higher carcinoembryonic antigen (CEA) but lower
carbohydrate antigen 19-9 (CA19-9) positivity, and
higher metastasis rate.[15] Another study from Japan
reviewed 209 PDAC patients and showed that patients
with pancreatic body/tail cancer were significantly
more likely to have abdominal pain but less likely to
have jaundice.[16] Other studies confirmed that patients
with pancreatic body/tail cancer were more likely to be
diagnosed at an advanced stage.[11, 17] SEER registries
database (1973-2002) reported that patients with
pancreatic body/tail cancer have a higher proportion of
the distant stage diseases (72.7%) compared to patients
with pancreatic head cancer (39.2%).[11]
Diabetes is a risk factor of pancreatic cancer. A
meta-analysis demonstrated that individuals in whom
diabetes had only recently been diagnosed (<4 years)
exhibited a 50% higher risk of the malignancy compared
with individuals who had diabetes for ≥5 years.[18] On
the other hand, pancreatic cancer can induce a diabetic
status.[18] Theoretically, patients with pancreatic body/
tail cancer are more prone to have islet dysfunction and
subsequent diabetes, since islet concentration is much
higher in the tail than in the head of the pancreas. But the
data comparing the onset of pancreatic cancer-induced
diabetes between the head, body, and tail of the pancreas
are limited. Of note, postoperative diabetes may be
higher in patients receiving distal pancreatectomy than
those treated with pancreaticoduodenectomy.[19]
Perfusion computed tomography (CT) and dynamic
contrast-enhanced magnetic resonance imaging (DCEMRI) can provide important information in the
diagnosis of pancreatic cancer. Perfusion CT allows
measurement of tumor vascular physiology including
tumor blood flow (BF), blood volume (BV), mean transit
time, and vascular permeability surface area product
(PS).[20] It has been reported that no significant difference
in perfusion values (BF, BV and PS) was found between
the head, body, and tail of the pancreas.[20, 21] However,
there is lack of studies comparing the imaging modalities
between the head, body, and tail of the pancreas.
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Hepatobiliary & Pancreatic Diseases International
Survival
It is not surprising that pancreatic head cancer has a
better overall patient survival than pancreatic body/tail
cancer, because more patients with pancreatic body/tail
cancer are diagnosed at a relatively advanced stage.
Data from SEER database (1988-2004) including 33 752
patients with pancreatic cancer presented a significantly
lower rate of cancer-related surgery (16% vs 30%) and
also a significant lower median survival (4 months vs 6
months) in patients with body/tail cancer compared with
those with head cancer.[22] The SEER registries database
(1973-2002) including 43 706 cases of pancreatic cancer
showed that pancreatic head cancer had a 4% lower
overall mortality risk compared with pancreatic body/
tail cancer in multivariate COX analysis.[11] However,
not consistent with the results from Western countries,
data from the National Pancreatic Cancer Registry of
Japan showed a significantly lower 5-year survival rate
(10.7% vs 13.8%) for patients with pancreatic head
cancer (n=5788) than those with pancreatic body/tail
cancer (n=1629).[13]
As long as operation is possible, pancreatic head
cancer is surgically treated by pancreaticoduodenectomy,
whereas pancreatic body/tail cancer is treated by a
distal pancreatectomy. As mentioned above, more
tumors are diagnosed at an early stage and the
resectability is higher in pancreatic head cancer. The
SEER database (1988-2004) including 5118 and 663
patients with resected pancreatic head and body/tail
cancers, respectively, revealed that tumor location at the
body/tail of the pancreas was an independent negative
predictor of survival in patients after surgery.[22] Of note,
most of the patients undergoing resection were not at
an early stage: 53% showed with regional lymph node
metastasis and 74% were at T-stage 3/4.[22] Within the
same local-stage, pancreatic head cancer had a much
lower 3-year survival rate than pancreatic body/tail
cancer (9% vs 20%).[11] Moreover, a Japanese study
enrolling 80 consecutive patients with resectable
pancreatic cancers presented similar overall survival
and recurrence rates after a curative resection between
patients with pancreatic head cancer (n=56) and those
with pancreatic body/tail cancer (n=24).[23]
Although surgical resection remains to be the only
potential cure for PDAC, only a small proportion of
patients newly diagnosed with PDAC are considered
for surgical resection. Chemo- and/or radiotherapy
has emerged as a key factor to improve patient
outcome. A retrospective study from Japan including
66 patients with metastatic PDAC who were treated
with gemcitabine revealed tumor location at the head
of the pancreas as an independent risk factor of poor
prognosis after chemotherapy.[24] Similarly, a study from
France using a cohort of 42 patients with metastatic
PDAC treated by fluorouracil/leucovorin combined
with irinotecan and oxaliplatin (FOLFIRINOX)
demonstrated that only tumor location in the head
of the pancreas was associated with poor outcome.[25]
However, some other reports showed that tumor site
(head vs body/tail) did not relate to progression freesurvival or overall survival in patients with advanced or
metastatic pancreatic cancer treated with chemo- and/
or radiotherapy.[26-28] So far, no large-sample and welldesigned study has yet been conducted for comparing
the different response to chemo- and/or radiotherapy
such as toxicity and tumor progression between different
tumor sites. The association between tumor localization
and response to chemo- and/or radiotherapy needs to
be further evaluated.
Diagnostic characterization of genetic markers
Microarray-based approaches have allowed genomewide, high throughput screening for novel candidate
genes or microRNAs (miRNAs) involved in the
pathogenesis of PDAC. Most recently, as a consequence
of technical advances, whole sequencing of the cancer
exome has been performed and leads to a greater insight
into the mutational spectrum of human cancers. In
2008, a comprehensive genetic analysis containing 24
PDACs determined an average of 63 genetic alterations
in the sequences of 23 219 transcripts, representing
20 661 protein-coding genes. These alterations defined a
core set of 12 cellular signaling pathways and processes
implicated in the deregulation that gives rise to the
major features of pancreatic tumorigenesis.[29] When
the data from 24 PDAC patients (head/tail: 19/5) were
correlated with several clinical parameters (e.g. age,
gender, tumor location), no significant difference
was found in the numbers of mutations (63.1±32.7 vs
72.6 ±24.0 per tumor), deletions (8.4±4.8 vs 7.8±3.1
per tumor), or amplifications (5.2±6.0 vs 9.0 ±10.9 per
tumor) between pancreatic head and tail cancers.[30]
However, details on point mutations in relation to
topology were not given and the study cohort was not
appropriately matched between patients with pancreatic
head and tail cancers.
The incidence of K-ras point mutations was not
different significantly between pancreatic head cancer
(79%, 22/28) and body/tail cancer (72%, 13/18) as
shown by combining the data from a Japanese and a
Chinese study.[31, 32] A recent report from USA described
2 patients presented with synchronous PDACs arising
from intraductal papillary mucinous neoplasm
(each with one tumor in the head and the other in
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Diversity between pancreatic head and body/tail cancers
the tail of the pancreas). They found both tumors
from each patient shared identical K-ras mutations
but different clonal genetic instability as reflected
by loss of heterozygosity analysis, indicating that
molecular diversity existed between tumors at different
localizations even if the synchronous tumors are likely
initiated from the same precursor lesions.[33]
MicroRNAs play key roles in diverse biological
processes, and accordingly, unique expression profiles of
miRNAs have been found in PDAC. Aberrant expression
of a number of miRNAs was closely associated with
tumor development, infiltration, metastasis and poor
prognosis.[34, 35] However, no study has taken tumor
location into consideration as part of the miRNA
analysis to date. We could only obtain the data on
circulating miR-210 expression from a study containing
16 and 6 patients with locally advanced unresectable
stage T4 PDACs in the head and body of the pancreas,
respectively. Here, miR-210 was found to be higher in
patients with pancreatic body cancer than those with
pancreatic head cancer.[36] Given the lack of detailed
information on potential genetic differences between
pancreatic head and body/tail cancers, we propose an in
vitro system based on the comparison of two PDAC cell
lines in the following section.
is an initial step in metastasis, whereas extracellular
matrix (ECM) adhesion is a key mediator in cell motility.
Therefore, comparing the ability of cell adhesion,
migration and invasion between Panc-1 and MIA PaCa-2
might help in discovering the metastatic potential of
pancreatic head and body/tail cancers. Compared to
MIA PaCa-2, Panc-1 showed a higher binding affinity
to collagens (type I and IV), the most abundant protein
in ECM, and also exhibited higher adhesion ability to
endothelial cells.[38, 39] In addition, Panc-1 expressed
greater levels of a series of cell adhesion molecules such
as E-selectin, intercellular adhesion molecule-1 (ICAM-1),
sialyl Lewis a (sLea), sialyl Lewis x (sLex), lymphocyte
function-associated antigen-1 (LFA-1) and very late
activation antigen-4 (VLA-4).[39] Moreover, Panc-1
exhibited much higher expression of invasion-associated
molecules than MIA PaCa-2, such as EphA2.[40]
Actually, invasion is a consequence of the cross talk
that occurs between cancer cells and stroma cells. For
better mimicking of the tumor environment, a study
using a co-culture system with PDAC cells and tumorderived fibroblasts demonstrated that hepatocyte
growth factor produced by fibroblasts could initiate an
apparent invasion-stimulating response in strongly c-met
expressing Panc-1 cells but not in weakly expressing
MIA PaCa-2 cells.[41] In this sense, pancreatic head
cancer (Panc-1) showed higher metastatic potential than
pancreatic body/tail cancer (MIA PaCa-2).
Comparison of pancreatic cancer cell lines
originating from pancreatic head and body/ Pro-angiogenic potential
tail cancers
Angiogenesis is critical for tumor growth and
Cancer cell lines reflect the genomic events leading to
tumor changes seen in clinical tissues and are valuable
tools in studies of tumor cell biology.[37] Different PDAC
cell lines arising from primary tumors, liver metastasis,
ascites, or lymph node metastasis exhibit a great deal
of diversity in structure and function. To compare the
cell lines derived from pancreatic head and body/tail
cancers, we reviewed current information characterizing
frequently used PDAC cell lines originating from the
primary tumors (BxPC-3, Capan-2, MIA PaCa-2 and
Panc-1). Other well known cell lines such as PSN-1 and
Panc Tu-1, which were derived from primary tumor but
the exact site of origin was not defined, were not included.
Panc-1 and MIA PaCa-2, the source of which are
matched by donor age (±10 years), tumor stage, histological
differentiation and ultrastructural features,[37, 38] were
selected as representing pancreatic head and body/tail
cancers, respectively.
Cell migration and invasion
Tumor cell motility is the hallmark of invasion and
metastasis. Vascular endothelial growth factor (VEGF),
which principally mediates angiogenesis, can determine
the angiogenic switch in cancer. Compared with Panc-1,
MIA PaCa-2 secreted lower levels of VEGF.[42] Both
Panc-1 and MIA PaCa-2 do not express cyclooxygenase-2
(COX-2) protein, an important mediator of angiogenesis
and tumor growth, which may indicate a relative low
pro-angiogenic potential.[38] However, comparison of
tumor-induced angiogenesis might be less important
because PDAC progression and prognosis have been
reported to be indeed angiogenesis independent.[43]
Tumorigenicity
Tumorigenicity in vivo is an efficient way for
evaluation of the tumor formation and metastatic
potential of cancer cells, and is commonly measured
by several parameters such as tumor mass, tumor size,
rate of growth and metastasis. However, the tumor
formation abilities varied among different methods,
such as subcutaneous cancer cell injection, intraperitoneal cancer cell injection, orthotopic tumor
Hepatobiliary Pancreat Dis Int，Vol 12，No 5 • October 15，2013 • www.hbpdint.com • 483
Hepatobiliary & Pancreatic Diseases International
implantation and orthotopic cancer cell injection
models.[38] Compared with other methods, orthotopic
injection of cancer cell better reflects the clinical
microenvironment and provides more convincing data.
In this model, both Panc-1 and MIA PaCa-2 presented
high intra-pancreatic tumorigenicity, local infiltration
and distant metastasis potential.[44, 45] However, data
directly comparing the orthotopic tumorigenicity of the
two PDAC cell lines are not yet given in this model.
By using immunohistochemical analysis, Panc-1
and MIA PaCa-2 tumors demonstrated quite similar
morphology, mucin accumulation, cytokeratin (CK)
profile (CK7/CK19, CK8/CK18 and CK20), trans
(vimentin, chr-A and α1-chym) and dedifferentiation
(pdx-1, shh and ptc) patterns.[46]
Chemo- and/or radiotherapy resistance
Chemo- and/or radiotherapy promote cancer cell
death primarily by the induction of apoptosis. A
number of studies have proven abundant evidence that
Panc-1 tolerates much higher half maximal inhibitory
concentration (IC50) values for 5-fluorouracil (5-FU)
and gemcitabine, and radiation than MIA PaCa-2.[47-49]
In addition, MIA PaCa-2 was more sensitive than
Panc-1 to oncolytic therapy and presented a dramatic
increase in apoptosis.[47] The possible reason was that
the expressions of anti-apoptotic proteins were much
higher in Panc-1 than those in MIA PaCa-2.[48, 49]
Ribonucleotide reductase M2 subunit (RRM2), a
gemcitabine-resistant enzyme, was also found to have
significantly higher expression in Panc-1 than MIA
PaCa-2.[50] Taken together, pancreatic head cancer
(Panc-1) is more chemo- and/or radio-resistant than
pancreatic body/tail cancer (MIA PaCa-2).
Genetic alterations and expression patterns
Genetic alterations in PDAC are common, both at
the cell and tissue levels. Cancer progression through
the accumulation of genetic alterations results in a gain
of cell growth and proliferation, and subsequently in
increased dissemination and metastatic potential. The
genetic basis of PDAC is usually elucidated using a
candidate gene approach, which has identified the four
most frequent mutations. Genetic defects exist in KRAS,
TP53 and CDKN2A/p16 genes but not in SMAD4/DPC4
in both cell lines.[37, 38, 45]
A meta-analysis including a consensus set of 2984
genes from four independent studies strictly compared
the gene expression profiles between PDAC and normal
pancreatic tissue, and found 62 differentially expressed
genes already known to associate with tumorigenesis
of PDAC.[51] Using this database,[51] we compared
the PDAC-associated gene profiles (http://www.
pancreasexpression.org/index.html) between Panc-1
and MIA PaCa-2, and found 52 differentially expressed
genes which had at least a 2-fold change in expression.
Fourteen out of the 52 genes have already been described
in detail (related PDAC cells function) and are presented
in Table 1.
Table 1. Differentially expressed PDAC-related genes in Panc-1 compared with MIA PaCa-2
Ensembl gene ID
Gene
symbol
Gene name
Function in Expression
Related cellular events
PDAC
profile
ENSG00000106541
AGR2
Anterior gradient homolog 2
Oncogenic
Up
Promotes dissemination of PDAC cells
ENSG00000111348
ARHGDIB Rho GDP dissociation inhibitor
(GDI) beta
Oncogenic
Up
Promotes invasion
ENSG00000062038
ENSG00000120885
ENSG00000116106
ENSG00000196611
ENSG00000099953
ENSG00000137673
ENSG00000181019
ENSG00000197956
CDH3
CLU
EPHA4
MMP1
MMP11
MMP7
NQO1
S100A6
Cadherin 3, type 1, P-cadherin
Clusterin
EPH receptor A4
Matrix metallopeptidase 1
Matrix metallopeptidase 11
Matrix metallopeptidase 7
NAD(P)H dehydrogenase, quinone 1
S100 calcium binding protein A6
Oncogenic
Oncogenic
Oncogenic
Oncogenic
Oncogenic
Oncogenic
Oncogenic
Oncogenic
Up
Up
Down
Down
Down
Up
Down
Down
Increases the motility of PDAC cells
Chemoresistance
Promotes PDAC cells growth
Extracellular matrix modulators
Extracellular matrix modulators
Extracellular matrix modulators
Cellular antioxidant
Increases the motility of PDAC cells
ENSG00000163993
S100P
S100 calcium binding protein P
Oncogenic
Up
Promotes PDAC cells growth, survival and
invasion
ENSG00000175793
ENSG00000113140
ENSG00000102265
SFN
SPARC
TIMP1
Stratifin
Oncogenic Up
Secreted protein, acidic, cysteine-rich Oncogenic Up
Tissue metallopeptidase inhibitor 1 Suppressive Down
Chemoresistance, promotes PDAC cells invasion
Promotes PDAC cells migration and invasion
Inhibits PDAC invasion
References can be provided by the authors on request. PDAC: pancreatic ductal adenocarcinoma.
484 • Hepatobiliary Pancreat Dis Int，Vol 12，No 5 • October 15，2013 • www.hbpdint.com
Diversity between pancreatic head and body/tail cancers
Table 2. Differentially expressed PDAC-related miRNAs in Panc-1 compared with MIA PaCa-2
miRNA
Function in
PDAC
Expression
profile
Validated
targets
Related cellular events
Let-7 family
miR-10a
miR-10b
miR-21
miR-155
miR-196a
miR-200
miR-217
Suppressive
Oncogenic
Oncogenic
Oncogenic
Oncogenic
Oncogenic
Suppressive
Suppressive
Up
Up
Up
Up Up
Up
Up
Down
RAS
HOXB1, 3
HOXD10
PDCD4, TIMP3
TP53INP1
HOXC8
SIP1
KRAS
Inhibits cell proliferation
Promotes tumor invasion and metastasis
Promotes tumor invasion
Induces chemoresistance, enhances invasion and angiogenesis
Inhibits apoptosis
Involves in tumor progression and predicts poor prognosis
Increases E-cadherin and inhibits EMT
Reduces tumor cell growth and anchorage-independent colony formation
References can be provided by the authors on request. PDAC: pancreatic ductal adenocarcinoma; EMT: epithelial mesenchymal transition.
MicroRNA profiles
Studies have shown specifically altered miRNAs
between PDAC cell lines and human pancreatic ductal
epithelium control cell lines, and between subgroups
of PDAC cell lines with different invasion or metastasis
properties.[52-54] From these studies covering a large
panel of miRNAs, we could find several differentially
expressed miRNAs between Panc-1 and MIA PaCa-2,
such as miR-10b, miR-15b, miR-18a, miR-21, miR-22,
miR-125, miR-155, miR-181 and miR-196a.[52, 54] Other
studies focusing on a limited number of miRNAs also
showed differentially expressed miRNAs between Panc-1
and MIA PaCa-2 such as miR-10a and miR-217.[55, 56]
The differentially expressed PDAC-related miRNAs as
elucidated to date between Panc-1 and MIA PaCa-2 are
shown in Table 2.
Conclusions
So far, not enough attention has been paid to the
molecular diversity between pancreatic head and body/
tail cancers and the overall information is limited. The
current clinical data support the higher incidence, easier
detection and better prognosis of pancreatic head cancer
compared with pancreatic body/tail cancer. However,
for tumors at the early stage, pancreatic head cancer
may be associated with a lower survival compared with
pancreatic body/tail cancer. Although previous reports
describe large cohorts of patients, the evidence is still
not so convincing because there is a lack of strictly
case-matched comparison between the two subtypes
of PDAC. In addition, race or environment may also
affect the diversity because of the different results from
Western and Eastern countries.
The frequently used PDAC cell lines Panc-1 and
MIA PaCa-2, which are matched by donor age (±10
years), tumor stage, histological differentiation and
ultrastructural features, to some extent might represent
pancreatic head and body/tail cancers. Compared with
MIA PaCa-2, Panc-1 is more chemo- and/or radioresistant, which is consistent with the clinical findings
that tumor located at the head is associated with poor
prognosis after chemotherapy. In addition, Panc-1 has
a greater potential of ECM adhesion and cell invasion
than MIA PaCa-2, and exhibits a more 'oncogenic'
profile.
In summary, we might emphasize that diversity
exists between pancreatic head and body/tail cancers.
This finding confirms the importance of subsite division
and supports the development of individual treatment
strategies. Further pioneering studies on strictly
matched patient tumor samples are needed for a deep
understanding of molecular diversity. Furthermore,
genetic animal models may be established in the future
to better consider specific topological differences in
pancreatic tissue microenvironment.
Contributors: ZSS and KH proposed the study conception and
design. LQ and XX drafted the manuscript. KH made a critical
revision of manuscript. ZSS is the guarantor.
Funding: This work was supported by grants from the Foundation
of Zhejiang Educational Committee (20110443), the Health Bureau
of Zhejiang provine (201233263), and the Pancreatic Cancer
Consortium Kiel (DFG).
Ethical approval: Not needed.
Competing interest: No benefits in any form have been received
or will be received from a commercial party related directly or
indirectly to the subject of this article.
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Received March 7, 2013
Accepted after revision July 6, 2013
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