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

Autor: Ying Tong, Jianjun Zhang, Qiang Xia, Ning Xu, Meng Sha, Seogsong Jeong, Bi‐jun Qiu, Lei Xia
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Cancer Research
Kaplan-Meier Estimate
Cholangiocarcinoma
Mice
0302 clinical medicine
Cancer-Associated Fibroblasts
Fibroblast activation protein
alpha
Cell Movement
intrahepatic cholangiocarcinoma
Tumor Microenvironment
α‐SMA
Medicine
Intrahepatic Cholangiocarcinoma
lymph node metastasis
Middle Aged
Prognosis
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Immunohistochemistry
Lymphangiogenesis
lymphangiogenesis
Oncology
030220 oncology & carcinogenesis
Disease Progression
Heterografts
Female
isolation
Adult
Stromal cell
lcsh:RC254-282
03 medical and health sciences
In vivo
Animals
Humans
Radiology
Nuclear Medicine and imaging
Actin
Aged
Cell Proliferation
Neoplasm Staging
Proportional Hazards Models
cancer‐associated fibroblasts
business.industry
In vitro
Disease Models
Animal
030104 developmental biology
Bile Duct Neoplasms
Cancer research
business
Biomarkers
Zdroj: Cancer Medicine, Vol 7, Iss 9, Pp 4665-4677 (2018)
ISSN: 2045-7634
DOI: 10.1002/cam4.1704
Popis: 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.
Databáze: OpenAIRE
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