Atsushi Masamune1, Shin Hamada2, Naoki Yoshida2, Tatsuhide Nabeshima2, Tooru Shimosegawa2. 1. Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. amasamune@med.tohoku.ac.jp. 2. Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
Abstract
BACKGROUND: The interaction between pancreatic cancer cells and pancreatic stellate cells plays a pivotal role in the progression of pancreatic cancer. Pyruvate kinase isozyme M2 is a key enzyme in glycolysis. Previous studies have shown that pyruvate kinase isozyme M2 is overexpressed in pancreatic cancer and that it regulates the aggressive behaviors of pancreatic cancer cells. AIMS: To clarify the role of pyruvate kinase isozyme M2 in the interactions between pancreatic cancer cells and pancreatic stellate cells. METHODS: Pyruvate kinase isozyme M2-knockdown pancreatic cancer cells (Panc-1 and SUIT-2 cells) and pancreatic stellate cells were generated by the introduction of small interfering RNA-expressing vector against pyruvate kinase isozyme M2. Cell proliferation, migration, and epithelial-mesenchymal transition were examined in vitro. The impact of pyruvate kinase isozyme M2 knockdown on the growth of subcutaneous tumors was examined in nude mice in vivo. RESULTS: Pyruvate kinase isozyme M2-kockdown pancreatic cancer cells and pancreatic stellate cells showed decreased proliferation and migration compared to their respective control cells. Pancreatic stellate cell-induced proliferation, migration, and epithelial-mesenchymal transition were inhibited when pyruvate kinase isozyme M2 expression was knocked down in pancreatic cancer cells. In vivo, co-injection of pancreatic stellate cells increased the size of the tumor developed by the control SUIT-2 cells, but the effects were less evident when pyruvate kinase isozyme M2 was knocked down in SUIT-2 cells or pancreatic stellate cells. CONCLUSIONS: Our results suggested a critical role of pyruvate kinase isozyme M2 in the interaction between pancreatic cancer cells and pancreatic stellate cells.
BACKGROUND: The interaction between pancreatic cancer cells and pancreatic stellate cells plays a pivotal role in the progression of pancreatic cancer. Pyruvate kinase isozyme M2 is a key enzyme in glycolysis. Previous studies have shown that pyruvate kinase isozyme M2 is overexpressed in pancreatic cancer and that it regulates the aggressive behaviors of pancreatic cancer cells. AIMS: To clarify the role of pyruvate kinase isozyme M2 in the interactions between pancreatic cancer cells and pancreatic stellate cells. METHODS: Pyruvate kinase isozyme M2-knockdown pancreatic cancer cells (Panc-1 and SUIT-2 cells) and pancreatic stellate cells were generated by the introduction of small interfering RNA-expressing vector against pyruvate kinase isozyme M2. Cell proliferation, migration, and epithelial-mesenchymal transition were examined in vitro. The impact of pyruvate kinase isozyme M2 knockdown on the growth of subcutaneous tumors was examined in nude mice in vivo. RESULTS: Pyruvate kinase isozyme M2-kockdown pancreatic cancer cells and pancreatic stellate cells showed decreased proliferation and migration compared to their respective control cells. Pancreatic stellate cell-induced proliferation, migration, and epithelial-mesenchymal transition were inhibited when pyruvate kinase isozyme M2 expression was knocked down in pancreatic cancer cells. In vivo, co-injection of pancreatic stellate cells increased the size of the tumor developed by the control SUIT-2 cells, but the effects were less evident when pyruvate kinase isozyme M2 was knocked down in SUIT-2 cells or pancreatic stellate cells. CONCLUSIONS: Our results suggested a critical role of pyruvate kinase isozyme M2 in the interaction between pancreatic cancer cells and pancreatic stellate cells.
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