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

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 (alpha 3, beta 3 and gamma 2) in cell proliferation, migration, invasion, apoptosis and the epithelial-to-mesenchymal transition (EMT) in cancer. The roles of the alpha 3, beta 3 and gamma 2 subunits in the malignant biological behavior of PDAC were investigated in the present study. It was revealed that the alpha 3, beta 3 and gamma 2 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 (alpha 3) had a stronger effect on cell proliferation, migration and invasion. In addition, LAMB3 (beta 3) knockdown significantly increased E-cadherin levels and decreased vimentin levels, indicating that LAMB3 was associated with EMT. Likewise, LAMC2 (gamma 2) 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 (alpha 3, beta 3 and gamma 2) may be novel therapeutic targets of PDAC in the future.