PLoS pathogens, 2019-05, Vol.15 (5), p.e1007818
2019
Details
- Autor(en) / Beteiligte
- Titel
- Clonorchis sinensis excretory-secretory products increase malignant characteristics of cholangiocarcinoma cells in three-dimensional co-culture with biliary ductal plates
- Ist Teil von
- PLoS pathogens, 2019-05, Vol.15 (5), p.e1007818
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Clonorchis sinensis is a carcinogenic human liver fluke, prolonged infection which provokes chronic inflammation, epithelial hyperplasia, periductal fibrosis, and even cholangiocarcinoma (CCA). These effects are driven by direct physical damage caused by the worms, as well as chemical irritation from their excretory-secretory products (ESPs) in the bile duct and surrounding liver tissues. We investigated the C. sinensis ESP-mediated malignant features of CCA cells (HuCCT1) in a three-dimensional microfluidic culture model that mimics an in vitro tumor microenvironment. This system consisted of a type I collagen extracellular matrix, applied ESPs, GFP-labeled HuCCT1 cells and quiescent biliary ductal plates formed by normal cholangiocytes (H69 cells). HuCCT1 cells were attracted by a gradient of ESPs in a concentration-dependent manner and migrated in the direction of the ESPs. Meanwhile, single cell invasion by HuCCT1 cells increased independently of the direction of the ESP gradient. ESP treatment resulted in elevated secretion of interleukin-6 (IL-6) and transforming growth factor-beta1 (TGF-β1) by H69 cells and a cadherin switch (decrease in E-cadherin/increase in N-cadherin expression) in HuCCT1 cells, indicating an increase in epithelial-mesenchymal transition-like changes by HuCCT1 cells. Our findings suggest that C. sinensis ESPs promote the progression of CCA in a tumor microenvironment via the interaction between normal cholangiocytes and CCA cells. These observations broaden our understanding of the progression of CCA caused by liver fluke infection and suggest a new approach for the development of chemotherapeutic for this infectious cancer.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1553-7374, 1553-7366eISSN: 1553-7374DOI: 10.1371/journal.ppat.1007818Titel-ID: cdi_plos_journals_2251157788
- Format
- –
- Schlagworte
- Animals, Bile, Bile Duct Neoplasms - metabolism, Bile Duct Neoplasms - parasitology, Bile Duct Neoplasms - pathology, Bile ducts, Bile Ducts - metabolism, Bile Ducts - parasitology, Bile Ducts - pathology, Biliary tract cancer, Biology and Life Sciences, Cancer, Carcinogens, Care and treatment, Cell adhesion & migration, Cell culture, Cell Culture Techniques, Cells, Cultured, Chemotherapy, Cholangiocarcinoma, Cholangiocarcinoma - metabolism, Cholangiocarcinoma - parasitology, Cholangiocarcinoma - pathology, Chronic infection, Clonorchiasis - metabolism, Clonorchiasis - parasitology, Clonorchis sinensis, Clonorchis sinensis - pathogenicity, Coculture Techniques, Collagen (type I), Concentration gradient, Cytokines, Development and progression, Disease, E-cadherin, Engineering and Technology, Extracellular matrix, Fibrosis, Growth factors, Helminth Proteins - metabolism, Helminth Proteins - toxicity, Humans, Hydrogels, Hyperplasia, Infections, Inflammation, Interleukin 6, Irritation, Kinases, Life sciences, Liver, Male, Mechanical engineering, Medicine, Medicine and Health Sciences, Mesenchyme, Metastasis, Microfluidics, N-Cadherin, Organic chemistry, Oriental liver fluke, Physical Sciences, Physiology, Plates, Rabbits, Risk factors, Three dimensional models, Transforming growth factor-b1, Tumor Cells, Cultured, Tumor necrosis factor-TNF, Tumors