Abstract
Objective:Annexin A1 (ANXA1) is a calcium-dependent phospholipid-binding protein which contributes to proliferation, cancer progression and metastasis. Overexpression of ANXA1 is closely associated with metastasis in numerous types of cancer. Cholangiocarcinoma (CCA) is a bile-duct cancer which has high rates of metastasis. Previously, we demonstrated up-regulation of ANXA1 in a highly metastatic CCA cell line (KKU-213AL5). Here, we investigated the functions of ANXA1 in the progression of CCA cell lines and evaluated its clinical impacts in human CCA tissues. Methods: Effects of ANXA1 on metastatic potential of CCA cell lines were evaluated using cell-proliferation, clonogenic, migration and invasion assays. The expression of ANXA1 in 44 intrahepatic human CCA tissues was investigated using immunohistochemistry (IHC). The association of ANXA1 with clinicopathological features of CCA patients was analyzed. Results:Silencing of ANXA1 expression using siRNA significantly decreased cell proliferation, colony formation, cell migration and invasion in the KKU-213AL5 cell line. IHC results showed low expression of ANXA1 in normal bile ducts in the non-tumor area. In contrast, high expression of ANXA1 in human CCA tissues was associated with advanced tumor stage, tumor size and presence of lymph-node metastasis. Conclusion:These findings strongly imply that ANXA1 contributes to the progression of CCA. ANXA1 can serve as a potential prognostic marker for CCA. Ablation of ANXA1 action may be an alternative strategy to prevent metastasis of CCA.
Highlights
Cholangiocarcinoma (CCA) is a bile duct cancer which is difficult to diagnose at an early stage
Annexin A1 (ANXA1) expression levels in KKU-213A and KKU-213AL5 CCA cell lines were compared at the mRNA level using real-time PCR and at the protein level using western blot
Association of ANXA1 expression with metastatic properties of KKU-213AL5 was confirmed in the xenograft tissues
Summary
Cholangiocarcinoma (CCA) is a bile duct cancer which is difficult to diagnose at an early stage. Its high invasiveness and frequent metastasis contribute to the devastat¬ing prognosis and notoriously high mortality rate of CCA (Zeng and Tao, 2015). Complete resection is the only option for a cure. Only a very small proportion of CCA patients can receive such surgery (Luvira et al, 2016). Metastasis has already occurred in about 80% of CCA patients at diagnosis. These patients usually receive ineffective chemotherapy or palliative treatments (Butthongkomvong et al, 2013). There is little understanding of the molecular processes involved in metastasis in CCA that might give clues leading to a more effective treatment of this highly metastatic cancer
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