ARTICLE
Auteur(s) : A
Arfaoui-Toumi1, L Kria-Ben Mahmoud1,
M Ben Hmida2, M-T Khalfallah3, S
Regaya-Mzabi4, S Bouraoui1,4
1Mongi Slim Hospital, Laboratory of colorectal
cancer research UR03ES04, Tunis, Tunisia
2Medicine University Tunis, Department
of epidemiology and preventive medicine, Tunisia
3Mongi Slim Hospital, Department of surgery, Tunis,
Tunisia
4Mongi Slim Hospital, Department of Pathology,
Division of Cellular Oncology, La Marsa, Tunis,
Tunisia
Article reçu le 3 Juin 2009, accepté le 18 Novembre 2009
Introduction
Colorectal cancer is the fourth commonest form of cancer occurring
worldwide, with an estimated 783 000 new cases diagnosed
in 1990, the most recent year for which international estimates are
available [1]. It affects men and women almost equally, with about
400 000 cases in men annually and 381 000 in
women [1]. Large differences exist in survival, according to the
stage of disease. It is estimated that 394 000 deaths
from colorectal cancer still occur worldwide annually, and
colorectal cancer is the second common cause of death from any
cancer in men in the European Union [1, 2].
To date, the TNM classification remains the only factor widely
approved. But thanks to the progress of fundamental and
translational research, it appears clearly that more clinical and
molecular markers should be available soon to help the physician in
the management of colorectal cancer.
In this frame, due to the potential of galectins to participate
in many essential functions, it is only to be expected that this
lectin family should be involved in pathological expression. To
date, 14 different galectins have been characterized; they are
numbered according to the chronology of discovery
(galectin-1 to galectin-14) and widely distributed from lower
to higher vertebrates [3].
Human galectin-3 (gal-3) is a protein encoded by a gene
localized on chromosome 14q21-22 [4]. It has a molecular weight of
approximately 30,000 Daltons [4, 5] and is composed of two
domains; the NH2-terminal domain contains only 12 amino-acid
residues that control its cellular targeting, and the COOH-terminal
domain contains the carbohydrate recognition domain consisting of
140 amino-acid residues, which define the molecule as a
galectine [6-8]. This molecule is a member of the
β-galactoside-binding proteins. It is an intracellular and
extracellular lectin which interacts with intracellular
glycoproteins, cell surface molecules and extracellular matrix
proteins [9-11]. gal-3 is present in the nucleus and cytoplasm and
on the cell surface of murine and human cancer cells [12]. It is
widely expressed in epithelial and immune cells and its expression
is correlated with cancer aggressiveness and metastasis [5, 6].
gal-3 is involved in various biological processes including cell
growth, adhesion, differentiation, angiogenesis, apoptosis, and RNA
splicing [13, 14]. Recently, many authors have shown that gal-3 can
be a reliable diagnostic marker in many cancers and one of the
target proteins in cancer treatment [15].
The significance of gal-3 expression has already been evaluated
in many neoplasms. gal-3 is indeed up-regulated in cancers of
thyroid, liver, stomach, and tongue [16-18]. In contrast, it is
down-regulated in cancers of ovary, uterus, and breast [19-22]. For
other neoplasm, such as colon cancer, results on the role of gal-3
are conflicting, as some authors have shown an increase of the
protein expression, while others have shown a decrease [23-25].
Similarly, the prognostic value of gal-3 expression in colon
carcinoma differed between investigators. In fact, it has been
shown a worse survival rate in cases where gal-3 is over-expressed,
while others showed the opposite [14]. On the other hand, gal-3
localization in the normal colonic cells and the malignant cells
has been studied. Lee et al., found that gal-3 is present on
the surface of a variety of cultured colon cancer cells, with
preferential expression on the poorly-differentiated cell lines
[26]. Similarly, Irimura et al. found a higher content of
gal-3 in Dukes D-stage carcinomas compared with earlier stage
tumors, and that the protein is present in the cytoplasm of normal
epithelial cells [27]. However, Lotz et al. observed a
reduction in the amount of protein expressed in colon carcinoma
compared with the normal colonic mucosa that was accompanied by a
translocation of the protein from the nucleus to the cytoplasm
during malignant progression [23]. Thus, these conflicting data led
as to investigate gal-3 involvement in colon carcinomas. Moreover,
we have carried on an exhaustive literature search and found no
publication as of today on the role of gal-3 in the mucinous
colorectal carcinoma.
In this work, we intend:
- – to study the profile of gal-3 expression;
- – to determine whether it would represent a prognostic
factor for all colon adenocarcinomas;
- – finally to check whether it is involved in any stage
of colon carcinogenesis.
Materials and methods
Our immunohistochemical study aims to evaluate the of gal-3
expression comparatively on a set of 200 cases of colorectal
adenocarcinomas. Our set was subdivided into three groups:
40 mucinous carcinomas, 30 adenocarcinomas with mucinous
component less than 50%, and 130 non mucinous adenocarcinomas.
Adenocarcinomas with mucinous component have been selected
following slide rereading, because according to the World Health
Organization (WHO) classification, an adenocarcinoma with a
mucinous component lower than 50% of tumor volume is considered as
a non mucinous adenocarcinoma.
Immunohistochemistry: tissues and sections with formalin-fixed
and paraffin-embedded tumor tissues blocks were incubated in an
oven at 37°C over night, and were then deparaffinized in toluene
and hydrated in descending concentrations of ethanol (2 x 100%
for 5min and 95% for 5min), and finally in double-distilled water
(ddH2O). The activity of endogenous peroxidase was
blocked in 3% H2O2 in ddH2O for
10min. To expose masked epitopes, the sections were microwaved in
citrate buffer (pH = 6.0) twice for 5min each, then kept at room
temperature for 20min, followed by a Tris buffer wash for 2min, and
then washed three times in Tris buffer. The primary antibody; mouse
monoclonal anti-galectin-3, clone 9C4 (Diagnostic Biosystems,
MA, USA) was added at a proportion of 1:50 in antibody diluent
(DakoCytomation, Denmark), and then incubated at 4°C over night.
After washing with Tris buffer, the antibody binding was detected
by incubating the sections at room temperature with the
peroxidase-labelled DAKO Envision System (DakoCytomation, Denmark)
for 30min, using diaminobenzidine as a chromogene for 20min. After
washing with ddH2O, the sections were then
counterstained with haematoxylin. Two independent investigators,
without any knowledge of the clinical and histological data, graded
the slides in a blinded fashion. The cases were graded as
negative/weak, moderate or strong, based on the staining intensity.
The staining patterns were graded as membranous, cytoplasmic, or
nuclear. The percentage of the staining was graded as follows: <
10, from 10 to 25, from 25 to 50, from 50 to 75, and
> 75%. Finally, the staining intensity was compared between the
available samples of distant, adjacent normal mucosa, primary
tumor, and metastases when they are present from the same patient.
In the cases with discrepant scoring, a consensus score was reached
after re-examination. To avoid artificial effects, cells in areas
with necrosis, poor morphology or at the margins of sections were
not counted.
Statistical analysis: Statistical analysis was performed using
SPSS software. Associations between variables were tested with the
X2 test. A probability (p) value of less than
0.05 was considered to be statistically significant.
Results
Immunohistochemical analysis showed that expression of gal-3 was
intense and diffuse, and almost constantly cytoplasmic with
membranous reinforcement in normal mucosa and in the
well-differentiated adenocarcinoma (figure 1). We also found no
significant difference in terms of intensity and distribution of
gal-3 in the adjacent (figure 1) and distanced
normal mucosa (p > 0.05), (figure 2). When we take
into account only the intensity of gal-3, our results are quite
similar for the well-differentiated non mucinous adenocarcinomas in
both their superficial (figure 3A) and deep
components (figure
3B). However, we note a progressive decrease of the
membranous reinforcement of gal-3 when tumor infiltration goes
beyond the submucosa (figure 3B). When comparing
well-differentiated, moderately-differentiated, and
poorly-differentiated tumors, we note a change of gal-3 expression
that goes from the membrane and the cytoplasm, to cytoplasm and the
nucleus, until her becomes exclusively nuclear (figure 3A, C and D). In
adenocarcinomas with independent cells, we showed that gal-3 was
completely absent independently of its degree of infiltration
(figure 4).
As to mucinous adenocarcinomas, we found that gal-3 expression
decreases meaningfully in intensity and distribution in the
mucinous component of the tumor when compared to the adjacent
normal mucosa and to mucinous-free territories (p < 0.001),
(figure 5A and
B). gal-3 completely disappears in depth when tumor
structures existing within mucus are poorly-differentiated or
containing independent cells (figure 5B and C), as it is
the case of the non-mucinous adenocarcinoma with independent cells
(figure 4).
When mucinous carcinomas are composed of better-differentiated
structures, glanduliform, cribriform or partially cohesive cells
making gland segments surrounded by mucus, gal-3 positivity,
although discrete, is essentially nuclear and weakly cytoplasmic
(figure 5D). In
the mucinous carcinomas with independent cells (ring cells), we
found a steep and complete negativity of gal-3 in the tumor cells
when compared to the normal mucosa (figure 5C).
These observations are reinforced by the fact that in
adenocarcinomas with mucinous component less than 50%, that the WHO
integrates in the non mucinous adenocarcinoma subtype, the positive
staining of gal-3 persists in well-differentiated areas (p =
0.558), and dramatically decreases or completely disappears in the
deep areas of the mucinous subtype (p < 0.001), (figure 6).
Concerning the lymph nodes and liver metastasis, we show that
gal-3 staining is quite similar to the primary tumor independently
of its histological subtype (data not shown). Furthermore, in the
adenocarcinoma with mucinous component less than 50%, we found an
increase in gal-3 expression in the metastasis when the latter ones
grow up from the non mucinous component of the tumor. However, we
showed a negative staining of gal-3 in metastasis when they take
birth from mucinous component of the tumor (data not shown).
The comparative analysis of pattern of gal-3 expression in the
three groups of adenocarcinomas does not show any significant
difference in gal-3 expression between mucinous adenocarcinoma and
adenocarcinoma with mucinous component less than 50% (p = 0.509,
Table 1), since we note a decrease or a
complete absence of gal-3 in mucinous areas independently of its
proportion within the tumor. However, the profile of gal-3
expression between these two groups and the non mucinous
adenocarcinoma is significantly different (p < 0.001, Table 1).
We also found that every time that a mucinous component was
present, independently of its proportion, vascular embols were very
frequent and perineural invasion was almost constant (95%) when
compared to the non mucinous adenocarcinomas in which these
histoprognostic factors were observed in only 51% of cases (p <
0.001). On the other hand, 41% of these mucinous carcinomas and
adenocarcinomas with mucinous component are usually advanced stage
(C stage of Astler-Coller).
Table 1 Profile of gal-3 expression between the three
groups of adenocarcinoma: non mucinous, mucinous and adenocarcinoma
with mucinous component.
|
|
Intensity %
|
|
Distribution %
|
|
|
Weak
|
Moderate
|
Strong
|
P
|
<10
|
10 -> 25
|
25 -> 50
|
50 -> 75
|
>75
|
P
|
|
ADK
|
|
|
|
|
|
|
|
|
|
|
|
healthy mucosa
|
8
|
32
|
60
|
0,359 NS
|
0
|
6
|
14
|
2
|
38
|
0,36 NS
|
|
tumoral mucosa
|
6
|
42
|
52
|
|
0
|
5
|
5
|
4
|
39
|
|
|
|
|
|
|
|
|
|
|
|
|
|
CM
|
|
|
|
|
|
|
|
|
|
|
|
healthy mucosa
|
2,9
|
23,5
|
73,5
|
0,001 S
|
0
|
0
|
2,9
|
2,9
|
94
|
0,001 S
|
|
tumoral mucosa
|
82,3
|
5,8
|
11,7
|
|
61
|
5,8
|
20,5
|
3
|
8,8
|
|
|
|
|
|
|
|
|
|
|
|
|
|
CCM
|
|
|
|
|
|
|
|
|
|
|
|
healthy mucosa
|
0
|
22,7
|
77,3
|
0,001 S
|
0
|
0
|
0
|
0
|
100
|
0,026 S
|
|
tumoral mucosa
|
81,8
|
18,2
|
0
|
|
50
|
9,1
|
18,2
|
13,6
|
9,1
|
|
Discussion
Colon cancer occupies the fourth rank among all types of cancers
[1] and the first gastro-intestinal cancer by organ location [27,
28]. It constitutes an actual public health issue [28, 29].
Regarding colorectal carcinoma, some conflicting data were
reported. Some studies showed higher levels of gal-3 in colon
neoplasm in comparison to the normal mucosa, but also that over
expression is associated with advanced tumor stages and shorter
survival [1, 11, 24, 28]. In contrast, other studies reported
decreasing gal-3 levels in colon progression [1, 23]. In this
present study, we sought to investigate the involvement of gal-3 in
colorectal cancer development in the different histological subtype
of tumor (mucinous vs non mucinous carcinomas), while interesting
to adenocarcinoma with mucinous component less than 50%.
To this end, we immunohistochemically analysed the expression
profile of gal-3. We found that gal-3 was expressed with similar
manner in term of intensity and distribution in normal mucosa
distanced and adjacent to the tumor and in well differentiated
adenocarcinoma as it has been shown by Shimamura et al. in
adenocarcinomas of the pancreas [30]. However, the membranous
reinforcement of gal-3 in both tumor and normal tissue we described
herein (figure
1) has never been reported before. Nevertheless, it has
been shown a preferential localization of gal-3 as granular
inclusions at the apical side of the T84 human colon carcinoma
cell line [31].
Inside the tumor, our results are quite similar for the
well-differentiated non mucinous adenocarcinomas in both their
superficial (figure
3A) and deep components (figure 3B) when gal-3
intensity is studied. However, we note a progressive decrease of
the membranous reinforcement of gal-3 when tumor infiltration goes
beyond the submucosa (figure 3B). These findings
are worth-mentioning as they have never been reported before in any
kind of cancer and because they have an important impact in terms
of local aggressiveness.
Also, we reported here a progressive decrease of gal-3 according
to the decreasing degree of differentiation and a total negativity
in adenocarcinoma with independent cells especially in mucinous
carcinoma and in adenocarcinoma with mucinous component less than
50%. Furthermore, these histological subtypes showed to have
advanced stage of tumor and presented a higher metastatic potential
that constitute one of the most important factors of death [6].
These data, suggest that the loss of gal-3 was correlated to the
loss of cell adhesion. This data was supported by the previous
study of Hittelet et al. [32]. He demonstrated that not only
gal-3, but also gal-1 were involved in malignant progression
of colon cancer and he proved their role in regulation of cell
migration. Indeed, he showed that the 2 galectins: gal-3 and
gal-1 act at different sites to reduce cell migration and that
addition of the immune serum containing anti-gal-3 and
anti-gal-1 antibodies in cultured cell lines neutralized at
different manner their effect on cell migration, increasing the
MRDO (Maximum Relative Distance to the origin) [32]. Thus, these
data suggest that gal-3 might be involved in the modulation of
cell-cell and cell-matrix interactions, decreasing the motile
properties of colon cancer cells. However, according to our
results, the decrease of tumoral differentiation and the total loss
of cell cohesion in adenocarcinoma with independent cells, was
correlated to the decreasing of gal-3 expression in term of
intensity and distribution, especially its disappears from the
membrane and secondary from the cytoplasm. This can be in part
explained by a progressive decrease of gal-3 activity. Indeed,
cells don’t undergo a control on cellular adhesion. Those cells
don’t bind to the others what proves the extreme case of
adenocarcinoma with independent cell. Moreover, this can be the
consequence of the cleavage of gal-3 by metalloproteinases
especially on cell-surface and so a decreased level of gal-3
immunoreactivity. Furthermore, it has been showed that the
truncated version of gal-3 has a different affinity for ligands by
the action of metalloproteinases [32, 33]. The cleavage of gal-3
therefore impairs the homodimerization feature and confirms the
decrease of cellular adhesion. Moreover, there is a possibility
that this cleavage may have some role in tumor metastasis because
increased expression of metalloproteinase, especially MMP-2, is
known to be associated with tumor aggressiveness [6, 34]. On the
other hand, this cleavage induces the homotypic aggregation of
gal-3, resulting in tumor embolism, and increases metastatic
potential [6]. This can explain the frequent vascular embols and
perineural invasion observed in mucinous and in adenocarcinoma with
mucinous component < 50% in our present study. Thus, it
certainly exists a direct relation between the decreasing level of
gal-3, the loss of cell adhesion, the mucin secretion and the
presence of metastasis since it have been reported that
Muc2 (the major secreted mucin in mucinous carcinoma) was the
major ligand of gal-3 [35, 36].
Furthermore, it has been shown that prognostic/or diagnostic
value of galectins in colon tissue cannot be restricted to gal-3
and gal-1. Indeed, Nagy et al. have previously demonstrated
that gal-8 appeared to be higher in normal cases and adenomas
than in carcinomas, and showed that gal-8 exerts an inhibitory
influence on the migration of slowly groing human colon cancer
cells (HCT-15 and CoLo 201), and not on that of rapidly
growing ones (LoVo and DLD-1) [37]. This can be explained by the
fact that cancers associated with a high TNM level are thought to
express significantly higher metalloproteinase levels than colon
cancers associated with low TNM level.
Otherwise, molecular defects can explain the pattern of gal-3
expression. Many of these defects consist of mutations in key
classes of genes governing many biological processes such as the
galectins. Those mutations alter the amount or behaviors of the
proteins encoded by regulating genes and in so doing, disrupt
functions that control cell adhesion
To the best of our knowledge, we are the first to report on
gal-3 expression in terms of distribution and intensity of the
protein in adenocarcinomas with mucinous component less than 50%.
One study has addressed the question of adenocarcinomas with
mucinous component versus the non-mucinous ones, though, studying
only cell cycle proteins (p53 and p16), DNA repair proteins
(MLH1), and other proteins such as cyclooxygenase-2 and
O-6-methylguanine DNA methyltransferase, but not Gal-3 [38].
Thus, when we study the comparative analysis of gal-3 expression
profile in the three groups of tumors, we didn’t find any
significant difference in gal-3 expression between mucinous
adenocarcinoma and adenocarcinoma with mucinous component less than
50%, since we noted a decrease or even a complete absence of gal-3
in mucinous areas no matter their proportion within the tumor.
However, the profile of gal-3 expression between these two groups
taken together and the non mucinous adenocarcinoma is significantly
different (Table 1).
Consequently, our data led us to think whether it would be more
judicious to integrate colon carcinomas with mucinous component
less than 50% in the mucinous carcinomas, so that together these
two categories may constitute a spectrum of lesions with increasing
severity depending on the proportion of the mucinous component and
the degree of cell cohesion. Another question that needs our
attention is the existence of proteins downstream of gal-3 that
might play an important role in colon carcinogenesis. The
identification of such proteins will certainly give important
insights to colon carcinogenesis and will ultimately lead to new
drug discoveries.
Acknowledgements
We thank Dr. Sami Gritli for help with manuscript preparation and
Dr. Néjib Ben Hamida for statistical analysis.
Disclosure and conflicts. There is no conflict of
interest of any kind between the authors of this paper.
Références
1 Sablin MP, Italiano A, Spano JP. Colorectal
cancers: prognostic and predictive factors of response to
treatment. Bull Cancer 2009; 96: 417-23.
2 Kountourakis P, Pavlakis K, Psyrri A,
Rontogianni D, Xiros N, Patsouris E, et al.
Prognostic significance of HER3 and HER4 protein expression in
colorectal adenocarcinomas. BMC Cancer 2006; 6: 46.
3 Danguy A, Camby I, Kiss R. Galectins and
cancer. Biochim Biophys Acta 2002; 1572: 285-93.
4 Raimond J, Zimonjic DB, Mignon C,
Mattei M, Popescu NC, Monsigny M, et al.
Mapping of the galectin-3 gene (LGALS3) to human chromosome 14 at
region 14q21-22. Mamm Genome 1997; 9: 706-7.
5 Liu FT, Hsu DK, Zuberi RI, Kuwabara I,
Chi EY, Henderson WR. Expression and function of
galectin-3, a β galactoside-binging Lectin, in human monocytes and
macrophages. Am J Pathol 1995; 147: 1016-28.
6 Takenaka Y, Fukumori T, Raz A. Galectin-3 and
metastasis. Glycoconj J 2004; 19: 543-9.
7 Brondes SH, Cooper DN, Gitt MA, Leffler H.
Galectins. Structure and function of a large family of animal
lectins. J Biol Chem 1994; 19: 20807-10.
8 Gong HC, Honjo Y, Nangia-Makker P,
Hogan V, Mazurak N, Bresalier RS, et al. The
NH2 terminus of galectin-3 governs cellular compartimentalization
and fuction in cancer cells. Cancer Res 1999; 15: 6239-45.
9 Patterson RJ, Wang W, Wang JL. Understanding
the biochemical activities of galectin-1 and galectin-3 in the
nucleus. Glycoconj J 2004; 19: 499-506.
10 Lahm H, André S, Hoeflich A, Kaltner H,
Siebert HC, Sordat B, et al. Tumor galectinology:
insights into the complex network of a family of endogenous
lectins. Glycoconj J 2004; 20: 227-38.
11 Guévremont M, Martel-Pelletier J, Boileau C,
Liu FT, Richard M, Fernandes JC, et al.
Galectin-3 surface expression on human adult chondrocytes: a
potential substrate for collagenase-3. Ann Rheum Dis 2004; 63:
636-43.
12 Schoeppner HL, Raz A, Ho SB,
Bresalier RS. Expression of endogenous galactose-binding
lectin correlates with neoplastic progression in the colon. Cancer
1995; 75: 2818-26.
13 Nagy N, Legendre H, Engels O, André S,
Kaltner H, Wasano K, et al. Refined prognostic
evaluation in colon carcinoma using immunohistochemical galectin
fingerprinting. Cancer 2003; 97: 1849-58.
14 Park JW, Voss PG, Grabski S, Wang JL,
Patterson RJ. Association of galectin-1 and galectin-3 with
Gemin4 in complexes containing the SMN protein. Nucleic Acids Res
2001; 27: 3595-602.
15 Legendre H, Decaestecker C, Nagy N,
Hendlisz A, Schüring MP, Salmon I, et al.
Prognostic values of galectin-3 and the macrophage migration
inhibitory factor (MIF) in human colorectal cancers. Mod Pathol
2003; 16: 491-504.
16 Hsu DK, Dowling CA, Jeng KC, Chen JT,
Yang RY, Liu FT. Galectin-3 expression is induced in
cirrhotic liver and hepatocellular carcinoma. Int J Cancer 1999;
81: 519-26.
17 Honjo Y, Inohara H, Akahani S, Yoshii T,
Takenaka Y, Yoshida J, et al. Expression of
cytoplasmic galectin-3 as a prognostic marker in tongue carcinoma.
Clin Cancer Res 2000; 6: 4635-40.
18 Inohara H, Honjo Y, Yoshii T, Akahani S,
Yoshida J, Hattori K, et al. Expression of
galectin-3 in fine-needle aspirates as a diagnostic marker
differentiating benign from malignant thyroid neoplasms. Cancer
1999; 85: 2475-84.
19 Castronovo V, Van Den Brûle FA, Jackers P,
Clausse N, Liu FT, Gillet C, et al. Decreased
expression of galectin-3 is associated with progression of human
breast cancer. J Pathol 1996; 179: 43-8.
20 Idikio H. Galectin-3 expression in human breast
carcinoma: correlation with cancer histologic grade. Int J Oncol
1998; 12: 1287-90.
21 Van den Brûle FA, Berchuck A, Bast RC,
Liu FT, Gillet C, Sobel ME, et al. Differential
expression of the 67-kD laminin receptor and 31-kD human
laminin-binding protein in human ovarian carcinomas. Eur J Cancer
1994; 8: 1096-9.
22 van den Brule FA, Buicu C, Berchuck A,
Bast RC, Deprez M, Liu FT, et al. Expression of
the 67-kD laminin receptor, galectin-1, and galectin-3 in advanced
human uterine adenocarcinoma. Hum Pathol 1996; 27: 1185-91.
23 Lotz MM, Andrews Jr CW, Korzelius CA,
Lee EC, Steele Jr GD, Clarke A, et al.
Decreased expression of Mac-2 (carbohydrate binding protein 35) and
loss of its nuclear localization are associated with the neoplastic
progression of colon carcinoma. Proc Natl Acad Sci USA 1993; 90:
3466-70.
24 Castronovo V, Campo E, van den Brûle FA,
Claysmith AP, Cioce V, Liu FT, et al. Inverse
modulation of steady-state messenger RNA levels of two non-integrin
laminin-binding proteins in human colon carcinoma. J Natl Cancer
Inst 1992; 84: 1161-9.
25 Sanjuán X, Fernández PL, Castells A,
Castronovo V, van den Brule F, Liu FT, et al.
Differential expression of galectin 3 and galectin 1 in colorectal
cancer progression. Gastroenterology 1997; 113: 1906-15.
26 Lee EC, Woo HJ, Korzelius CA,
Steele Jr GD, Mercurio AM. Carbohydrate-binding
protein 35 is the major cell-surface laminin-binding protein in
colon carcinoma. Arch Surg 1991; 126: 1498-502.
27 Irimura T, Matsushita Y, Sutton RC,
Carralero D, Ohannesian DW, Cleary KR, et al.
Increased content of an endogenous lactose-binding lectin in human
colorectal carcinoma progressed to metastatic stages. Cancer Res
1991; 51: 387-93.
28 Goh KL, Quek KF, Yeo GT, Hilmi IN,
Lee CK, Hasnida N, et al. Colorectal cancer in
Asians: a demographic and anatomic survey in Malaysian patients
undergoing colonoscopy. Aliment Pharmacol Ther 2005; 22:
859-64.
29 Bresalier RS, Mazurek N, Sternberg LR,
Byrd JC, Yunker CK, Nangia-Makker P, et al.
Metastasis of human colon cancer is altered by modifying expression
of the beta-galactoside-binding protein galectin 3.
Gastroenterology 1998; 115: 287-96.
30 Shimamura T, Sakamoto M, Ino Y,
Shimada K, Kosuge T, Sato Y, et al.
Clinicopathological significance of galectin-3 expression in ductal
adenocarcinoma of the pancreas. Clin Cancer Res 2002; 8:
2570-5.
31 Huflejt ME, Jordan ET, Gitt MA,
Barondes SH, Leffler H. Strikingly different localization
galectin-3 and galectin-4 in human colon adenocarcinoma T84 cells.
Am Soc Biochem Mol Biol 1996; 272: 14294-303.
32 Hittelet A, Legendre H, Nagy N,
Bronckart Y, Pector JC, Salmon I, et al.
Upregulation of galectins-1 and -3 in human colon cancer and their
role in regulating cell migration. Int J Cancer 2003; 103:
370-9.
33 Ochieng J, Green B, Evans S, James O,
Warfield P. Modulation of the biologic functions of galectin-3
by matrix metalloproteinases. Biochim Biophys Acta 1998; 1379:
97-106.
34 Chen WT. Critical appraisal of the use of matrix
metalloproteinase inhibitors in cancer treatment. Oncogene 2000;
19: 6642-50.
35 Dudas SP, Yunker CK, Sternberg LR,
Byrd JC, Bresalier RS. Expression of human intestinal
mucin is modulated by the beta-galactoside binding protein
galectin-3 in colon cancer. Gastroenterology 2002; 123: 817-26.
36 Bresalier RS, Byrd JC, Wang L, Raz A.
Colon cancer mucin: a new ligand for the beta-galactoside-binding
protein galectin-3. Cancer Res 1996; 56: 4354-7.
37 Nagy N, Bronckart Y, Camby I, Legendre H,
Lahm H, Kaltner H, et al. Galectin-8 expression
decreases in cancer compared with normal and dysplastic human colon
tissue and acts significantly on human colon cancer cell migration
as a suppressor. Gut 2002; 50: 392-401.
38 Ogino S, Brahmandam M, Cantor M,
Namgyal C, Kawasaki T, Kirkner G, et al.
Distinct molecular features of colorectal carcinoma with signet
ring cell component and colorectal carcinoma with mucinous
component. Mod Pathol 2006; 19: 59-68.
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