Journal
CANCER MEDICINE
Volume 7, Issue 9, Pages 4665-4677Publisher
WILEY
DOI: 10.1002/cam4.1704
Keywords
alpha-SMA; cancer-associated fibroblasts; intrahepatic cholangiocarcinoma; isolation; lymph node metastasis; lymphangiogenesis
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Funding
- National Natural Science Foundation of China [81472243, 81670598]
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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-beta. 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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