Contributions of ADAM12 via HB-EGF/EGFR signaling cascades to EMT and cancer progression in pancreas

Abstract

Abstract Background Pancreatic cancer (PC) is one of the most malignant tumors with a 5-year survival rate of less than 7% in China. High amount of stroma and activation of epithelial-mesenchymal transition (EMT) in PC induce drug resistance and poor prognosis. Aims The objective of the present study was to prove impaction of a disintegrin and metalloproteinase 12 (ADAM12) via Heparin-binding EGF-like growth factor (HB-EGF)/EGFR signalling pathway on EMT and cancer development in PC. Methods 62 pancreatic specimens were collected from two hospitals by surgical resection, of which 43 were tumor specimens. All samples were analysed by immunohistochemistry. Results Consistent with GEPIA database, the expression of ADAM12, as well as HB-EGF, was significantly upregulated in 43 PC tissues compared with other 19 benign pancreatic mass. We also found that high expressions of ADAM12 and HB-EGF were significantly correlated with lymph node metastasis, advanced TNM stage and poor survival. Besides, high expression of ADAM12 was correlated with the upregulation of EGFR and EMT markers. Conclusion Together our data demonstrate that ADAM12 is associated with PC progression and may contribute to shedding of HB-EGF, inducing EMT through EGFR pathway. These suggest that inhibition of ADAM12/HB-EGF/EGFR signal pathway may be capable to be a therapeutic method, which requires further in vivo and vitro studies to explore the mechanism.