KAI1 inhibits lymphangiogenesis and lymphatic metastasis of pancreatic cancerin vivo

摘要

BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but its mechanism is not clear. The present study  aimed  to  determine  the  role  of  KAI1  in  lymphatic metastasis, speciifcally in pancreatic cancer. METHODS: The KAI1 gene was transfected into the pancreatic cancer cell line MIA PaCa-2 and PANC-1 by using liposomes and selected by G418, and the protein was measured by Western blotting. After successful infection, the cell growth curve was studied by MTT, vascular endothelial growth factor C (VEGF-C) secretion by pancreatic cancer cell were measured by ELISA. The KAI1 and pCMV transfected MIA PaCa-2 cells were renamed as MIA PaCa-2-K and MIA PaCa-2-p. These two kinds of cells were injected into the subcuticular layer of nude mice; both tumor growth and metastasis through the lymphatic nodes were assessed. Lymphangiogenesis in tumors was measured by immunohistochemistry. RESULTS: The  VEGF-C  secretion  was  signiifcantly  reduced in MIA PaCa-2 cells compared with PANC-1 cells after being transfected with the KAI1 gene. The growth rate of subcutaneous tumors was similar after the injection of MIA PaCa-2-K, MIA PaCa-2, and MIA PaCa-2-p. MIA PaCa-2-K tumors showed slower lymphangiogenesis and lymph node metastasis compared with MIA PaCa-2 and MIA PaCa-2-p tumors. CONCLUSION: The  overexpression  of  KAI1  inhibits  the lymphangiogenesis and lymph node metastasis of MIA PaCa-2 pancreatic tumors.