Laminin-332 mediates proliferation, apoptosis, invasion, migration and epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma

Abstract

The poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) is primarily due to the invasive and metastatic behaviors of this disease. Laminin-332 (LM-332) is a key component of the basement membrane barrier, and is associated with tumor metastasis. The present study provides evidence towards the potential function of LM-332 in carcinoma, indicating the distinct roles of the three LM-332 subunits (α3, β3 and γ2) in cell proliferation, migration, invasion, apoptosis and the epithelial-to-mesenchymal transition (EMT) in cancer. The roles of the α3, β3 and γ2 subunits in the malignant biological behavior of PDAC were investigated in the present study. It was revealed that the α3, β3 and γ2 subunits were upregulated in PDAC. Inhibition of all LM-332 subunits abrogated the tumorigenic outcomes, which included cell proliferation, apoptosis, invasion, migration and EMT in vitro. However, the three LM-332 subunits had different degrees of effects on biological behavior. It was observed that LAMA3 (α3) had a stronger effect on cell proliferation, migration and invasion. In addition, LAMB3 (β3) knockdown significantly increased E-cadherin levels and decreased vimentin levels, indicating that LAMB3 was associated with EMT. Likewise, LAMC2 (γ2) mediated proliferation, apoptosis, invasion and migration. However, small interfering (si)-LAMC2 promoted the progression of EMT, which was the opposite effect to that of si-LAMB3. The LM-332 subunits (α3, β3 and γ2) may be novel therapeutic targets of PDAC in the future.