Platelet-derived PDGF promotes the invasion and metastasis of cholangiocarcinoma by upregulating MMP2/MMP9 expression and inducing EMT via the p38/MAPK signalling pathway.
Shuguang Pan, Ying Hu, Mengjia Hu, Hongmei Jian, Mo Chen, Lang Gan, Ping Zheng, Yu He, Junping Wang
Abstract
Cholangiocarcinoma (CCA) is an aggressive tumour with a poor prognosis due to its late clinical presentation and the lack of effective non-surgical therapies. Previous studies have reported that platelets are implicated in tumour invasion and metastasis, while their role and the underlying mechanism in CCA remain unclear. Here, we show that platelets are hyperactivated in patients with CCA and that platelet-derived growth factor (PDGF) promotes the migration of CCA tumour cells both in vitro and in vivo. Further investigations revealed that PDGF can upregulate the expression of MMP2/MMP9 and induce epithelial-mesenchymal transition (EMT) by activating the p38/MAPK signalling pathway in CCA cells. In addition, the expression of MMP2/MMP9 was associated with lymph node metastasis and poor prognosis in CCA patients after surgical resection. In conclusion, our findings demonstrate that platelets play an important role in facilitating the invasion and metastasis of CCA cells by secreting PDGF, which may provide a novel target for CCA treatment.