P Chen1, J Zhou2, J Li2, Q Zhang2, Q Zuo3. 1. Department of Orthopedics, Affiliated Yancheng Hospital, School of Medicine, Southeast University, Nanjing, 211189, China. 2. Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China. 3. Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, China. zuoqiang1985@njmu.edu.cn.
Abstract
BACKGROUND: Osteosarcoma is the most common primary malignancy of the bone, and macrophages play a promotional role during osteosarcoma development and progression. TIPE1 is known to function as a tumor suppressor in diverse cancers by inducing cell arrest and apoptosis. However, the biological function of TIPE1 in osteosarcoma is still unclear. PURPOSE: The purpose of this study was to investigate the expression and function of TIPE1 in osteosarcoma. METHODS: In the present study, TIPE1 expression in osteosarcoma cancer cells was determined by qPCR and western blotting. A subcutaneous tumor model was established to investigate the potential anti-tumor activity of TIPE1 in osteosarcoma. Further, flow cytometry, western blotting, immunofluorescence staining, and ELISA were performed to clarify the underlying mechanism by which TIPE1 regulates growth of osteosarcoma. RESULTS: Our results suggest that TIPE1 is downregulated in osteosarcoma cancer cells, and ectopic expression TIPE1 significantly inhibited osteosarcoma tumor growth in vivo. Furthermore, TIPE1 inhibits the infiltration of macrophages in osteosarcoma tumor by suppressing MCP-1 expression in osteosarcoma cells. Further in vivo study revealed that inhibition of MCP-1/CCR2 axis by Bindarit blocked the inhibitory effect of TIPE1 on osteosarcoma growth. CONCLUSION: Collectively, our results demonstrate the anti-tumor role of TIPE1 in osteosarcoma and reveal a novel therapy target for osteosarcoma.
BACKGROUND:Osteosarcoma is the most common primary malignancy of the bone, and macrophages play a promotional role during osteosarcoma development and progression. TIPE1 is known to function as a tumor suppressor in diverse cancers by inducing cell arrest and apoptosis. However, the biological function of TIPE1 in osteosarcoma is still unclear. PURPOSE: The purpose of this study was to investigate the expression and function of TIPE1 in osteosarcoma. METHODS: In the present study, TIPE1 expression in osteosarcoma cancer cells was determined by qPCR and western blotting. A subcutaneous tumor model was established to investigate the potential anti-tumor activity of TIPE1 in osteosarcoma. Further, flow cytometry, western blotting, immunofluorescence staining, and ELISA were performed to clarify the underlying mechanism by which TIPE1 regulates growth of osteosarcoma. RESULTS: Our results suggest that TIPE1 is downregulated in osteosarcoma cancer cells, and ectopic expression TIPE1 significantly inhibited osteosarcoma tumor growth in vivo. Furthermore, TIPE1 inhibits the infiltration of macrophages in osteosarcoma tumor by suppressing MCP-1 expression in osteosarcoma cells. Further in vivo study revealed that inhibition of MCP-1/CCR2 axis by Bindarit blocked the inhibitory effect of TIPE1 on osteosarcoma growth. CONCLUSION: Collectively, our results demonstrate the anti-tumor role of TIPE1 in osteosarcoma and reveal a novel therapy target for osteosarcoma.
Authors: J Sybil Biermann; Warren Chow; Damon R Reed; David Lucas; Douglas R Adkins; Mark Agulnik; Robert S Benjamin; Brian Brigman; G Thomas Budd; William T Curry; Aarati Didwania; Nicola Fabbri; Francis J Hornicek; Joseph B Kuechle; Dieter Lindskog; Joel Mayerson; Sean V McGarry; Lynn Million; Carol D Morris; Sujana Movva; Richard J O'Donnell; R Lor Randall; Peter Rose; Victor M Santana; Robert L Satcher; Herbert Schwartz; Herrick J Siegel; Katherine Thornton; Victor Villalobos; Mary Anne Bergman; Jillian L Scavone Journal: J Natl Compr Canc Netw Date: 2017-02 Impact factor: 11.908
Authors: Struan F A Grant; Andrew D Wells; Matthew C Pahl; Carole Le Coz; Chun Su; Prabhat Sharma; Rajan M Thomas; James A Pippin; Emylette Cruz Cabrera; Matthew E Johnson; Michelle E Leonard; Sumei Lu; Alessandra Chesi; Kathleen E Sullivan; Neil Romberg Journal: Genome Biol Date: 2022-06-03 Impact factor: 17.906