Introduction: Galectin-1 is a lectin with immunosuppressive effect in different solid tumors. We investigated galectin-1 expression in triple-negative breast cancer (TNBC) to determine its prognostic value. Methods: We examined 95 TNBC surgical samples in tissue microarrays with galectin-1 immunohistochemistry (intensity and percentage of staining) and looked for influences on overall and progression-free survivals (PFSs) with the help of Kaplan-Meier estimates. Univariable and multivariable Cox regressions were also analyzed. Results: According to Kaplan-Meier curves, a significantly worse overall survival (OS) was found for TNBC patients showing intense or ≥50% galectin-1 stromal interface staining versus those lacking it. Cox regression analyses suggested that galectin-1 expression was an independent prognosticator in TNBC. According to the quantity of stromal tumor-infiltrating lymphocytes (sTILs), significant survival differences depending on galectin-1 status were only seen in the low sTILs (<30%) subset. Multivariable analysis suggested that galectin-1 expression was an independent prognosticator for PFS. Discussion: The immunosuppressive effects of galectin-1 forming a shield around tumor nests may form an immune escape mechanism and can explain the worse OS and PFS we found in TNBC. Owing to the exploratory nature of the study, the results need confirmation in order to investigate the potentials of anti-galectin-1 therapies.

1.
Barondes
SH
,
Cooper
DN
,
Gitt
MA
,
Leffler
H
.
Galectins. Structure and function of a large family of animal lectins
.
J Biol Chem
.
1994
;
269
(
33
):
20807
10
.
2.
Perillo
NL
,
Marcus
ME
,
Baum
LG
.
Galectins: versatile modulators of cell adhesion, cell proliferation, and cell death
.
J Mol Med
.
1998
;
76
(
6
):
402
12
.
3.
Camby
I
,
Le Mercier
M
,
Lefranc
F
,
Kiss
R
.
Galectin-1: a small protein with major functions
.
Glycobiology
.
2006
;
16
(
11
):
137R
57R
.
4.
Hughes
RC
.
Secretion of the galectin family of mammalian carbohydrate-binding proteins
.
Biochim Biophys Acta
.
1999
;
1473
(
1
):
172
85
.
5.
Moutsatsos
IK
,
Wade
M
,
Schindler
M
,
Wang
JL
.
Endogenous lectins from cultured cells: nuclear localization of carbohydrate-binding protein 35 in proliferating 3T3 fibroblasts
.
Proc Natl Acad Sci USA
.
1987
;
84
(
18
):
6452
6
.
6.
Rabinovich
GA
.
Galectin-1 as a potential cancer target
.
Br J Cancer
.
2005
;
92
(
7
):
1188
92
.
7.
Akimoto
Y
,
Hirabayashi
J
,
Kasai
K
,
Hirano
H
.
Expression of the endogenous 14-kDa beta-galactoside-binding lectin galectin in normal human skin
.
Cell Tissue Res
.
1995
;
280
(
1
):
1
10
.
8.
Sato
S
,
Burdett
I
,
Hughes
RC
.
Secretion of the baby hamster kidney 30-kDa galactose-binding lectin from polarized and nonpolarized cells: a pathway independent of the endoplasmic reticulum-Golgi complex
.
Exp Cell Res
.
1993
;
207
(
1
):
8
18
.
9.
Shimonishi
T
,
Miyazaki
K
,
Kono
N
,
Sabit
H
,
Tuneyama
K
,
Harada
K
, et al
.
Expression of endogenous galectin-1 and galectin-3 in intrahepatic cholangiocarcinoma
.
Hum Pathol
.
2001
;
32
(
3
):
302
10
.
10.
Chetry
M
,
Song
Y
,
Pan
C
,
Li
R
,
Zhang
J
,
Zhu
X
.
Effects of galectin-1 on biological behavior in cervical cancer
.
J Cancer
.
2020
;
11
(
6
):
1584
95
.
11.
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
(
6
):
1906
15
.
12.
Gopalan
V
,
Saremi
N
,
Sullivan
E
,
Kabir
S
,
Lu
CT
,
Salajegheh
A
, et al
.
The expression profiles of the galectin gene family in colorectal adenocarcinomas
.
Hum Pathol
.
2016
;
53
:
105
13
.
13.
Chen
J
,
Tang
D
,
Wang
S
,
Li
QG
,
Zhang
JR
,
Li
P
, et al
.
High expressions of galectin-1 and VEGF are associated with poor prognosis in gastric cancer patients
.
Tumour Biol
.
2014
;
35
(
3
):
2513
9
.
14.
Rorive
S
,
Belot
N
,
Decaestecker
C
,
Lefranc
F
,
Gordower
L
,
Micik
S
, et al
.
Galectin-1 is highly expressed in human gliomas with relevance for modulation of invasion of tumor astrocytes into the brain parenchyma
.
Glia
.
2001
;
33
(
3
):
241
55
.
15.
Jung
TY
,
Jung
S
,
Ryu
HH
,
Jeong
YI
,
Jin
YH
,
Jin
SG
, et al
.
Role of galectin-1 in migration and invasion of human glioblastoma multiforme cell lines
.
J Neurosurg
.
2008
;
109
(
2
):
273
84
.
16.
Wu
H
,
Chen
P
,
Liao
R
,
Li
YW
,
Yi
Y
,
Wang
JX
, et al
.
Overexpression of galectin-1 is associated with poor prognosis in human hepatocellular carcinoma following resection
.
J Gastroenterol Hepatol
.
2012
;
27
(
8
):
1312
9
.
17.
Saussez
S
,
Decaestecker
C
,
Lorfevre
F
,
Cucu
DR
,
Mortuaire
G
,
Chevalier
D
, et al
.
High level of galectin-1 expression is a negative prognostic predictor of recurrence in laryngeal squamous cell carcinomas
.
Int J Oncol
.
2007
;
30
(
5
):
1109
17
.
18.
Carlini
MJ
,
Roitman
P
,
Nuñez
M
,
Pallotta
MG
,
Boggio
G
,
Smith
D
, et al
.
Clinical relevance of galectin-1 expression in non-small cell lung cancer patients
.
Lung Cancer
.
2014
;
84
(
1
):
73
8
.
19.
Ding
YM
,
Dong
JH
,
Chen
LL
,
Zhang
HD
.
Increased expression of galectin-1 is associated with human oral squamous cell carcinoma development
.
Oncol Rep
.
2009
;
21
(
4
):
983
7
.
20.
Kim
HJ
,
Jeon
HK
,
Cho
YJ
,
Park
YA
,
Choi
JJ
,
Do
IG
, et al
.
High galectin-1 expression correlates with poor prognosis and is involved in epithelial ovarian cancer proliferation and invasion
.
Eur J Cancer
.
2012
;
48
(
12
):
1914
21
.
21.
Orozco
CA
,
Martinez-Bosch
N
,
Guerrero
PE
,
Vinaixa
J
,
Dalotto-Moreno
T
,
Iglesias
M
, et al
.
Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk
.
Proc Natl Acad Sci USA
.
2018
;
115
(
16
):
E3769
78
.
22.
Bogut
A
,
Stojanovic
B
,
Jovanovic
M
,
Dimitrijevic Stojanovic
M
,
Gajovic
N
,
Stojanovic
BS
, et al
.
Galectin-1 in pancreatic ductal adenocarcinoma: bridging tumor biology, immune evasion, and therapeutic opportunities
.
Int J Mol Sci
.
2023
;
24
(
21
):
15500
.
23.
Laderach
DJ
,
Gentilini
LD
,
Giribaldi
L
,
Delgado
VC
,
Nugnes
L
,
Croci
D
, et al
.
A unique galectin signature in human prostate cancer progression suggests galectin-1 as a key target for treatment of advanced disease
.
Cancer Res
.
2013
;
73
(
1
):
86
96
.
24.
von Klot
CA
,
Kramer
MW
,
Peters
I
,
Hennenlotter
J
,
Abbas
M
,
Scherer
R
, et al
.
Galectin-1 and Galectin-3 mRNA expression in renal cell carcinoma
.
BMC Clin Pathol
.
2014
;
14
:
15
.
25.
Aboulhagag
NA
,
El-Deek
HEM
,
Sherif
MF
.
Expression of galectin-1 and galectin-3 in renal cell carcinoma; immunohistochemical study
.
Ann Diagn Pathol
.
2018
;
36
:
31
7
.
26.
Arcolia
V
,
Journe
F
,
Wattier
A
,
Leteurtre
E
,
Renaud
F
,
Gabius
HJ
, et al
.
Galectin-1 is a diagnostic marker involved in thyroid cancer progression
.
Int J Oncol
.
2017
;
51
(
3
):
760
70
.
27.
Shen
KH
,
Li
CF
,
Chien
LH
,
Huang
CH
,
Su
CC
,
Liao
AC
, et al
.
Role of galectin-1 in urinary bladder urothelial carcinoma cell invasion through the JNK pathway
.
Cancer Sci
.
2016
;
107
(
10
):
1390
8
.
28.
Dalotto-Moreno
T
,
Croci
DO
,
Cerliani
JP
,
Martinez-Allo
VC
,
Dergan-Dylon
S
,
Méndez-Huergo
SP
, et al
.
Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease
.
Cancer Res
.
2013
;
73
(
3
):
1107
17
.
29.
Geiger
P
,
Mayer
B
,
Wiest
I
,
Schulze
S
,
Jeschke
U
,
Weissenbacher
T
.
Binding of galectin-1 to breast cancer cells MCF7 induces apoptosis and inhibition of proliferation in vitro in a 2D- and 3D-cell culture model
.
BMC Cancer
.
2016
;
16
(
1
):
870
.
30.
Gao
Y
,
Li
X
,
Shu
Z
,
Zhang
K
,
Xue
X
,
Li
W
, et al
.
Nuclear galectin-1-FOXP3 interaction dampens the tumor-suppressive properties of FOXP3 in breast cancer
.
Cell Death Dis
.
2018
;
9
(
4
):
416
.
31.
Louka
ML
,
Said
H
,
El Sayed
S
,
El-Shinawi
M
.
Galectin 1 overexpression in breast cancer tissues: relation to serum matrix metalloproteinase 2 and 9 activity
.
Gene Rep
.
2017
;
7
:
184
8
.
32.
Grazier
JJ
,
Sylvester
PW
.
Role of galectins in metastatic breast cancer
. In:
Mayrovitz
HN
, editor.
Breast cancer
.
Brisbane (AU)
:
Exon Publications
;
2022
[Cited 2024 dec 27]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK583815/
33.
Cousin
JM
,
Cloninger
MJ
.
The role of galectin-1 in cancer progression, and synthetic multivalent systems for the study of galectin-1
.
Int J Mol Sci
.
2016
;
17
(
9
):
1566
.
34.
Huang
Y
,
Wang
HC
,
Zhao
J
,
Wu
MH
,
Shih
TC
.
Immunosuppressive roles of galectin-1 in the tumor microenvironment
.
Biomolecules
.
2021
;
11
(
10
):
1398
.
35.
Saussez
S
,
Camby
I
,
Toubeau
G
,
Kiss
R
.
Galectins as modulators of tumor progression in head and neck squamous cell carcinomas
.
Head Neck
.
2007
;
29
(
9
):
874
84
.
36.
Matarrese
P
,
Tinari
A
,
Mormone
E
,
Bianco
GA
,
Toscano
MA
,
Ascione
B
, et al
.
Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission
.
J Biol Chem
.
2005
;
280
(
8
):
6969
85
.
37.
Toscano
MA
,
Bianco
GA
,
Ilarregui
JM
,
Croci
DO
,
Correale
J
,
Hernandez
JD
, et al
.
Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death
.
Nat Immunol
.
2007
;
8
(
8
):
825
34
.
38.
Yu
X
,
Siegel
R
,
Roeder
RG
.
Interaction of the B cell-specific transcriptional coactivator OCA-B and galectin-1 and a possible role in regulating BCR-mediated B cell proliferation
.
J Biol Chem
.
2006
;
281
(
22
):
15505
16
.
39.
Rabinovich
GA
,
Ariel
A
,
Hershkoviz
R
,
Hirabayashi
J
,
Kasai
KI
,
Lider
O
.
Specific inhibition of T-cell adhesion to extracellular matrix and proinflammatory cytokine secretion by human recombinant galectin-1
.
Immunology
.
1999
;
97
(
1
):
100
6
.
40.
De Oliveira
JT
,
DE Matos
AJ
,
Barros
R
,
Ribeiro
C
,
Chen
A
,
Hespanhol
V
, et al
.
Differential expression of galectin-1 and galectin-3 in canine non-malignant and malignant mammary tissues and in progression to metastases in mammary tumors
.
Anticancer Res
.
2014
;
34
(
5
):
2211
21
.
41.
Hendry
S
,
Salgado
R
,
Gevaert
T
,
Russell
PA
,
John
T
,
Thapa
B
, et al
.
Assessing tumor-infiltrating lymphocytes in solid tumors: a practical review for pathologists and proposal for a standardized method from the international immunooncology biomarkers working group: Part 1: assessing the host immune response, TILs in invasive breast carcinoma and ductal carcinoma in situ, metastatic tumor deposits and areas for further research
.
Adv Anat Pathol
.
2017
;
24
(
5
):
235
51
.
42.
Loi
S
,
Drubay
D
,
Adams
S
,
Pruneri
G
,
Francis
PA
,
Lacroix-Triki
M
, et al
.
Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers
.
J Clin Oncol
.
2019
;
37
(
7
):
559
69
.
43.
Hanahan
D
,
Weinberg
RA
.
The hallmarks of cancer
.
Cell
.
2000
;
100
(
1
):
57
70
.
44.
Hanahan
D
,
Weinberg
RA
.
Hallmarks of cancer: the next generation
.
Cell
.
2011
;
144
(
5
):
646
74
.
45.
Rakha
EA
,
El-Sayed
ME
,
Green
AR
,
Lee
AH
,
Robertson
JF
,
Ellis
IO
.
Prognostic markers in triple-negative breast cancer
.
Cancer
.
2007
;
109
(
1
):
25
32
.
46.
El Bairi
K
,
Haynes
HR
,
Blackley
E
,
Fineberg
S
,
Shear
J
,
Turner
S
, et al
.
The tale of TILs in breast cancer: a report from the international immuno-oncology biomarker working group
.
NPJ Breast Cancer
.
2021
;
7
(
1
):
150
.
47.
Denkert
C
,
von Minckwitz
G
,
Darb-Esfahani
S
,
Lederer
B
,
Heppner
BI
,
Weber
KE
, et al
.
Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy
.
Lancet Oncol
.
2018
;
19
(
1
):
40
50
.
48.
Stanton
SE
,
Adams
S
,
Disis
ML
.
Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: a systematic review
.
JAMA Oncol
.
2016
;
2
(
10
):
1354
60
.
49.
Jung
EJ
,
Moon
HG
,
Cho
BI
,
Jeong
CY
,
Joo
YT
,
Lee
YJ
, et al
.
Galectin-1 expression in cancer-associated stromal cells correlates tumor invasiveness and tumor progression in breast cancer
.
Int J Cancer
.
2007
;
120
(
11
):
2331
8
.
You do not currently have access to this content.