Isolation of cancer‐associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma

Abstract Intrahepatic cholangiocarcinoma is a highly fatal tumor characterized by an abundant stromal environment. Cancer‐associated fibroblasts play key roles in tumor growth and invasiveness and have been regarded as a potential therapeutic target. This study was designed to isolate human primary...

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Main Authors: Meng Sha, Seogsong Jeong, Bi‐jun Qiu, Ying Tong, Lei Xia, Ning Xu, Jian‐jun Zhang, Qiang Xia
Format: Article
Language:English
Published: Wiley 2018-09-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.1704
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author Meng Sha
Seogsong Jeong
Bi‐jun Qiu
Ying Tong
Lei Xia
Ning Xu
Jian‐jun Zhang
Qiang Xia
author_facet Meng Sha
Seogsong Jeong
Bi‐jun Qiu
Ying Tong
Lei Xia
Ning Xu
Jian‐jun Zhang
Qiang Xia
author_sort Meng Sha
collection DOAJ
description Abstract Intrahepatic cholangiocarcinoma is a highly fatal tumor characterized by an abundant stromal environment. Cancer‐associated fibroblasts play key roles in tumor growth and invasiveness and have been regarded as a potential therapeutic target. This study was designed to isolate human primary cancer‐associated fibroblasts of intrahepatic cholangiocarcinoma to study tumor‐stroma interactions and to analyze the clinical relevance of alpha‐smooth muscle actin ‐positive cancer‐associated fibroblasts in patients with intrahepatic cholangiocarcinoma. The isolated cancer‐associated fibroblasts were positive for alpha‐smooth actin, fibroblast‐specific protein‐1, fibroblast activation protein, and PDGFR‐β. In addition, cancer‐associated fibroblasts were found to increase proliferation, migration, and invasion of cholangiocarcinoma cells in vitro and promote tumor growth of mice in vivo. Moreover, alpha‐smooth muscle actin‐positive expression of cancer‐associated fibroblasts predicted unfavorable prognosis in patients with intrahepatic cholangiocarcinoma and showed correlation with presence of lymph node metastasis. This study may provide a useful tool to investigate further effect of cancer‐associated fibroblasts on the molecular mechanism of cholangiocarcinoma cells as well as contribution of cancer‐associated fibroblasts in lymphangiogenesis and lymph node metastasis.
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spelling doaj-art-9887f1ae88af46df9c97f627cd341dc02025-08-20T03:07:27ZengWileyCancer Medicine2045-76342018-09-01794665467710.1002/cam4.1704Isolation of cancer‐associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinomaMeng Sha0Seogsong Jeong1Bi‐jun Qiu2Ying Tong3Lei Xia4Ning Xu5Jian‐jun Zhang6Qiang Xia7Department of Liver Surgery Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Liver Surgery Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Liver Surgery Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Liver Surgery Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Liver Surgery Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Liver Surgery Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Liver Surgery Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai ChinaDepartment of Liver Surgery Ren Ji Hospital School of Medicine Shanghai Jiao Tong University Shanghai ChinaAbstract Intrahepatic cholangiocarcinoma is a highly fatal tumor characterized by an abundant stromal environment. Cancer‐associated fibroblasts play key roles in tumor growth and invasiveness and have been regarded as a potential therapeutic target. This study was designed to isolate human primary cancer‐associated fibroblasts of intrahepatic cholangiocarcinoma to study tumor‐stroma interactions and to analyze the clinical relevance of alpha‐smooth muscle actin ‐positive cancer‐associated fibroblasts in patients with intrahepatic cholangiocarcinoma. The isolated cancer‐associated fibroblasts were positive for alpha‐smooth actin, fibroblast‐specific protein‐1, fibroblast activation protein, and PDGFR‐β. In addition, cancer‐associated fibroblasts were found to increase proliferation, migration, and invasion of cholangiocarcinoma cells in vitro and promote tumor growth of mice in vivo. Moreover, alpha‐smooth muscle actin‐positive expression of cancer‐associated fibroblasts predicted unfavorable prognosis in patients with intrahepatic cholangiocarcinoma and showed correlation with presence of lymph node metastasis. This study may provide a useful tool to investigate further effect of cancer‐associated fibroblasts on the molecular mechanism of cholangiocarcinoma cells as well as contribution of cancer‐associated fibroblasts in lymphangiogenesis and lymph node metastasis.https://doi.org/10.1002/cam4.1704α‐SMAcancer‐associated fibroblastsintrahepatic cholangiocarcinomaisolationlymph node metastasislymphangiogenesis
spellingShingle Meng Sha
Seogsong Jeong
Bi‐jun Qiu
Ying Tong
Lei Xia
Ning Xu
Jian‐jun Zhang
Qiang Xia
Isolation of cancer‐associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma
Cancer Medicine
α‐SMA
cancer‐associated fibroblasts
intrahepatic cholangiocarcinoma
isolation
lymph node metastasis
lymphangiogenesis
title Isolation of cancer‐associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma
title_full Isolation of cancer‐associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma
title_fullStr Isolation of cancer‐associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma
title_full_unstemmed Isolation of cancer‐associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma
title_short Isolation of cancer‐associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma
title_sort isolation of cancer associated fibroblasts and its promotion to the progression of intrahepatic cholangiocarcinoma
topic α‐SMA
cancer‐associated fibroblasts
intrahepatic cholangiocarcinoma
isolation
lymph node metastasis
lymphangiogenesis
url https://doi.org/10.1002/cam4.1704
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