Integrating single‐cell and spatial analysis reveals MUC1‐mediated cellular crosstalk in mucinous colorectal adenocarcinoma
Clinical and Translational Medicine,
Год журнала:
2024,
Номер
14(5)
Опубликована: Май 1, 2024
Abstract
Background
Mucinous
colorectal
adenocarcinoma
(MCA)
is
a
distinct
subtype
of
cancer
(CRC)
with
the
most
aggressive
pattern,
but
effective
treatment
MCA
remains
challenge
due
to
its
vague
pathological
characteristics.
An
in‐depth
understanding
transcriptional
dynamics
at
cellular
level
critical
for
developing
specialised
strategies.
Methods
We
integrated
single‐cell
RNA
sequencing
and
spatial
transcriptomics
data
systematically
profile
tumor
microenvironment
(TME),
particularly
interactome
stromal
immune
cells.
In
addition,
three‐dimensional
bioprinting
technique,
canonical
ex
vivo
co‐culture
system,
immunofluorescence
staining
were
further
applied
validate
communication
networks
within
TME.
Results
This
study
identified
crucial
intercellular
interactions
that
engaged
in
pathogenesis.
found
increased
infiltration
FGF7
+
/
THBS1
myofibroblasts
tissues
decreased
expression
genes
associated
leukocyte‐mediated
immunity
T
cell
activation,
suggesting
role
these
cells
regulating
immunosuppressive
MS4A4A
macrophages
exhibit
M2‐phenotype
enriched
tumoral
niche
high
was
poor
prognosis
cohort
data.
The
ligand‐receptor‐based
analysis
revealed
tight
interaction
MUC1
malignant
ZEB1
endothelial
cells,
providing
mechanistic
information
angiogenesis
molecular
targets
subsequent
translational
applications.
Conclusions
Our
provides
novel
insights
into
communications
among
tumour
are
significantly
TME
during
progression,
presenting
potential
prognostic
biomarkers
therapeutic
strategies
MCA.
Key
points
Tumour
profiling
developed.
interplay
promote
development.
M2
phenotype
endotheliocytes
engage
EndMT
process
Язык: Английский
Effect of microenvironmental viscosity on the emergence of colon cancer cell resistance to doxorubicin
Journal of Materials Chemistry B,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Microenvironmental
viscosity
enhanced
doxorubicin
resistance
of
colon
cancer
cells.
Язык: Английский
Nutraceutical Evaluation of Trigonelline's Therapeutic Potential by Targeting Bladder Cancer Stem Cells and Cancer-Associated Fibroblasts via Downregulation of TGFβ3/GLI2/YAP1 Signaling Hub
International Journal of Medical Sciences,
Год журнала:
2025,
Номер
22(5), С. 1194 - 1207
Опубликована: Фев. 18, 2025
Trigonelline
(TGN),
an
alkaloid
identified
in
medicinal
plants
such
as
coffee
(Coffea
spp.)
and
fenugreek
(Trigonella
foenum-graecum),
has
demonstrated
significant
anticancer
properties
across
various
malignancies,
yet
its
efficacy
bladder
cancer
(BLCA)
remains
underappreciated.
This
study
investigates
TGN's
role
modulating
stem
cells
(CSCs)
the
tumor
microenvironment
(TME),
two
key
contributors
to
BLCA
progression
chemoresistance.
Through
comprehensive
bioinformatics
analyses
of
patient
datasets,
a
TGY
signature
(TGFβ3,
GLI2,
YAP1)
was
critical
signaling
hub
associated
with
poor
prognosis,
therapeutic
resistance,
CSC
generation.
Computational
docking
studies
revealed
high
binding
affinity
signature,
TGFβ3
(ΔG
=
-3.9
kcal/mol),
GLI2
-4.2
YAP1
-3.4
suggesting
potential
disrupt
this
axis.
In
vitro
experiments
that
TGN
effectively
inhibited
cell
proliferation,
colony
formation,
tumorspheroid
growth
while
significantly
enhancing
cisplatin
sensitivity
resistant
lines.
Notably,
reduced
transformation
fibroblasts
into
cancer-associated
(CAFs)
through
downregulation
α-SMA
FAP
(Fibroblast
activation
protein)
expression,
indicating
capacity
normalize
TME.
Real-time
PCR
analysis
treatment
markers
epithelial-mesenchymal
transition
stemness
pathways.
Our
preclinical
mouse
combining
tumorigenesis
cisplatin-resistant
tumoroids
harboring
CAFs.
Importantly,
combination
therapy
showed
no
apparent
systematic
toxicity,
favorable
safety
profile.
findings
reveal
novel
molecular
targets
cancer;
acts
potent
disruptor
axis
normalizer
TME
by
reducing
CAF
transformation.
sum,
our
advocate
for
further
exploration
candidate
drug-resistant
BLCA,
improve
outcomes
simultaneously
targeting
both
CSCs
TME,
serving
foundation
future
clinical
trials.
Язык: Английский
Spatial and single‐cell transcriptomic analysis reveals fibroblasts dependent immune environment in colorectal cancer
BioFactors,
Год журнала:
2025,
Номер
51(2)
Опубликована: Март 1, 2025
Abstract
Colorectal
cancer
(CRC)
exhibits
a
complex
tumor
microenvironment
with
significant
cellular
heterogeneity,
particularly
involving
cancer‐associated
fibroblasts
that
influence
behavior
and
metastasis.
This
study
integrated
single‐cell
RNA
sequencing
spatial
transcriptomics
to
dissect
fibroblast
heterogeneity
in
CRC.
Data
processing
employed
Seurat
for
quality
control,
principal
component
analysis
dimensionality
reduction,
t‐Distributed
Stochastic
Neighbor
Embedding
visualization.
Differentially
expressed
genes
were
identified
using
DESeq2.
Immune
infiltration
was
assessed
via
Single‐Sample
Gene
Set
Enrichment
Analysis,
CIBERSORT,
xCell
algorithms.
Prognostic
through
univariate
Cox
regression,
followed
by
consensus
clustering
survival
analysis.
Metabolic
pathways
explored
scMetabolism.
Experimental
validation
involved
CCK8,
scratch,
Transwell
assays
evaluate
the
roles
of
key
BGN
CERCAM
CRC
cell
proliferation
Machine
learning‐driven
four
fibroblast‐associated
(TRIP6,
TIMP1,
BGN,
CERCAM)
demonstrating
prognostic
relevance
Consensus
based
on
these
biomarkers
stratified
patients
into
three
distinct
molecular
subtypes
(Clusters
A–C).
Notably,
Cluster
C
exhibited
most
unfavorable
clinical
outcomes
coupled
marked
upregulation
all
fibroblast‐related
genes.
Comprehensive
immune
profiling
revealed
paradoxical
features
C:
heightened
global
activation
(characterized
substantial
leukocyte
infiltration)
coexisted
specific
immunosuppressive
elements,
including
enrichment
pro‐tumorigenic
M0
macrophages,
depletion
anti‐tumor
plasma
cells,
resting
memory
CD4+
T
along
coordinated
multiple
checkpoint
molecules.
Computational
prediction
TIDE
platform
suggested
enhanced
immunotherapy
responsiveness
patients.
Functional
demonstrated
knockdown
or
significantly
impaired
malignant
phenotypes,
reducing
proliferative
capacity,
migration
potential,
invasive
ability.
Fibroblasts
demonstrate
within
microenvironment,
impacting
prognosis
therapeutic
responses.
Key
emerge
as
potential
immunotherapeutic
targets,
offering
new
strategies
precision
treatment
Язык: Английский
Characterizing macrophage diversity in colorectal malignancies through single-cell genomics
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Март 21, 2025
Colorectal
cancer
(CRC)
is
one
of
the
most
common
malignant
tumors
digestive
tract,
with
increasing
incidence
and
mortality
rates,
posing
a
significant
burden
on
human
health.
Its
progression
relies
various
mechanisms,
among
which
tumor
microenvironment
tumor-associated
macrophages
(TAMs)
have
garnered
attention.
Macrophage
infiltration
in
solid
associated
poor
prognosis
linked
to
chemotherapy
resistance
many
cancers.
These
biological
behaviors
depend
heterogeneity
macrophages.
Tumor-promoting
TAMs
comprise
subpopulations
characterized
by
distinct
markers
unique
transcriptional
profiles,
rendering
them
potential
targets
for
anticancer
therapies
through
either
depletion
or
reprogramming
from
pro-tumoral
an
anti-tumoral
state.
Single-cell
RNA
sequencing
technology
has
significantly
enhanced
our
research
resolution,
breaking
traditional
simplistic
definitions
macrophage
subtypes
deepening
understanding
diversity
within
TAMs.
However,
unified
elucidation
nomenclature
molecular
characteristics
this
remains
lacking.
In
review,
we
assess
application
conventional
polarization
colorectal
malignancies
explore
several
defined
single-cell
omics
perspective
recent
years,
categorizing
based
their
functions.
Язык: Английский