Chen Wang1, Hong-Yu Li, Bin Liu, Sheng Huang, Li Wu, Ying-Yi Li. 1. Cancer Research Institute, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Abstract
BACKGROUND: As one of the most lethal cancers, pancreatic cancer presents poor prognosis with an overall 5-y survival of less than 5%. We previously reported that Pim-3, a member of the proto-oncogene Pim family that encodes serine/threonine kinases, is aberrantly expressed in human pancreatic cancer lesions. In the current study, we investigated the role of Pim-3 in promoting tumor growth and angiogenesis in an orthotopic nude mouse model of human pancreatic cancer. METHODS: We constructed retroviral vectors for human Pim-3 and a kinase-dead mutant of human Pim-3 (K69M); the retroviral supernatants generated from these vectors were then used to infect the human pancreatic cancer cell line MiaPaCa-2 to establish stable cell lines. We assessed cell proliferation using CCK-8, tumor growth, and angiogenesis in vivo in an orthotopic mouse model of pancreatic cancer. While tumor size was measured using magnetic resonance imaging, the tumor tissues were excised for protein extraction and histological analysis to detect vascular endothelium growth factor (VEGF) expression and vessel density. RESULTS: We established an orthotopic nude mouse model of human pancreatic cancer. We observed that Pim-3 promoted the proliferation of human pancreatic cancer cells, both in vitro and in vivo. Moreover, Pim-3 is required for vasculogenesis of primary human pancreatic tumors in vivo and promotion of angiogenesis through the induction of VEGF expression. CONCLUSIONS: Pim-3 can promote tumor growth and angiogenesis by stimulating the VEGF pathway.
BACKGROUND: As one of the most lethal cancers, pancreatic cancer presents poor prognosis with an overall 5-y survival of less than 5%. We previously reported that Pim-3, a member of the proto-oncogene Pim family that encodes serine/threonine kinases, is aberrantly expressed in humanpancreatic cancer lesions. In the current study, we investigated the role of Pim-3 in promoting tumor growth and angiogenesis in an orthotopic nude mouse model of humanpancreatic cancer. METHODS: We constructed retroviral vectors for humanPim-3 and a kinase-dead mutant of humanPim-3 (K69M); the retroviral supernatants generated from these vectors were then used to infect the humanpancreatic cancer cell line MiaPaCa-2 to establish stable cell lines. We assessed cell proliferation using CCK-8, tumor growth, and angiogenesis in vivo in an orthotopic mouse model of pancreatic cancer. While tumor size was measured using magnetic resonance imaging, the tumor tissues were excised for protein extraction and histological analysis to detect vascular endothelium growth factor (VEGF) expression and vessel density. RESULTS: We established an orthotopic nude mouse model of humanpancreatic cancer. We observed that Pim-3 promoted the proliferation of humanpancreatic cancer cells, both in vitro and in vivo. Moreover, Pim-3 is required for vasculogenesis of primary humanpancreatic tumors in vivo and promotion of angiogenesis through the induction of VEGF expression. CONCLUSIONS:Pim-3 can promote tumor growth and angiogenesis by stimulating the VEGF pathway.
Authors: Andrea L Casillas; Shailender S Chauhan; Rachel K Toth; Alva G Sainz; Amber N Clements; Corbin C Jensen; Paul R Langlais; Cindy K Miranti; Anne E Cress; Noel A Warfel Journal: Oncogene Date: 2021-07-02 Impact factor: 9.867