Abstract
Backgroud
Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumor microenvironment,
which play an important role in tumor progression. However, the mechanism is unclear.
Aims
To investigate the role of CAFs with HS6ST1-overexpression in cell migration and invasion
effects.
Methods
Human primary CAFs were isolated and identified from intrahepatic cholangiocarcinoma.
mRNA profiles differences between CAFs and NFs were examined by using transcriptome
sequencing. Using Transwell® migration assays, ICCA cells (RBE and HUCCT1) with NF-CM,
CAF-CM, CAFsNC-CM, and CAFsHS6ST1-CM were analyzed. Immunohistochemical staining were used to analyze the expression
of HS6ST1 in CAF in 152 patients with ICCA. Overall survival (OS) was compared based
on CAF HS6ST1 expression were analysed. The relationship between clinicopathological
parameters and survival was also examined.
Results
Successfully isolated CAFs is positive staining with αSMA, FSP-1, FAP, and PDGFR-β.
Transcriptome sequencing showed that differently expressed genes were enriched in
the function of the extracellular matrix and chemokine signaling pathway. HS6ST1 is
differentially expressed between CAFs and NFs, and associated with the migration and
invasion of ICCA cells. Moreover, HS6ST1 positive expression of CAFs predicted unfavorable
prognosis in patients with intrahepatic cholangiocarcinoma and showed correlation
with the presence of lymph node metastasis.
Conclusion
HS6ST1 is new possibilities for targeting the CAFs to reduce cholangiocarcinoma growth
and metastasis.
Keywords
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Article info
Publication history
Published online: December 29, 2022
Accepted:
December 7,
2022
Received:
May 5,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
