Abstract
Numerous experimental and epidemiological studies have demonstrated a correlation between Clonorchis sinensis (C. sinensis) infestation and cholangiocarcinoma (CCA). However, the role of C. sinensis in the increased invasiveness and proliferation involved in the malignancy of CCA has not been addressed yet. Here, we investigated the possibility that C. sinensis infestation promotes expression of focal and cell-cell adhesion proteins in CCA cells and secretion of matrix metalloproteinases (MMPs). Adhesion proteins help maintain cell aggregates, and MMPs promote the three-dimensional invasion of cells into the neighboring extracellular matrix (ECM). Using a novel microfluidic assay, we quantitatively addressed the role of excretory-secretory products (ESPs) gradients from C. sinensis in promoting the invasion of cells into the neighboring ECM.
Highlights
Cholangiocarcinoma (CCA) is a disastrous, highly lethal malignancy of the biliary tract whose poor prognosis reflects difficulties in making an early diagnosis and a lack of effective therapy [1,2,3]
It is currently estimated that 15– 20 million people are infected with C. sinensis, more than 200 million are at constant risk of infection [8], and 1.5–2.0 million show symptoms or complications of clonorchiasis
excretory-secretory products (ESPs) accumulated in the medium outside of the HuCCT1 tumor mass
Summary
Cholangiocarcinoma (CCA) is a disastrous, highly lethal malignancy of the biliary tract whose poor prognosis reflects difficulties in making an early diagnosis and a lack of effective therapy [1,2,3]. Risk factors for CCA are considered to include primary sclerosing cholangitis, fibropolycystic liver disease, intrahepatic biliary stones, chemical carcinogen exposure, viral hepatitis, and parasitic infestation. Many experimental and epidemiological studies have identified a strong correlation between liver fluke infestation and CCA [4,5,6]. Clonorchiasis, an infection by C. sinensis, the third-most prevalent worm parasite in the world, can be fatal, largely because of the associated long-term complication of CCA. It is currently estimated that 15– 20 million people are infected with C. sinensis, more than 200 million are at constant risk of infection [8], and 1.5–2.0 million show symptoms or complications of clonorchiasis. The International Agency for Research on Cancer (IARC) classified C. sinensis as a group I biological human carcinogen in 2009 [9,10]
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