TIPE1 suppresses osteosarcoma tumor growth by regulating macrophage infiltration
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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.
The purpose of this study was to investigate the expression and function of TIPE1 in osteosarcoma.
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.
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.
Collectively, our results demonstrate the anti-tumor role of TIPE1 in osteosarcoma and reveal a novel therapy target for osteosarcoma.
KeywordsOsteosarcoma TIPE1 Macrophages MCP-1
The present study was supported by Natural Science Foundation of Jiangsu Province (BK20161069).
PC and JCZ were involved in the acquisition of the data. JML and QZ were involved in the analysis and interpretation of the data. QZ was involved in the conception and design of the present study.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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