Interleukin-22 Promotes Osteosarcoma Cell Proliferation and Invasion via STAT3 Activation

Abstract

BackgroundInterleukin-22 (IL-22) is one of the cytokines secreted by T-helper 17 (Th17) cells. It belongs to the IL-10 cytokine family and influences a variety of immune reactions. Studies have indicated that IL-22 can promote cancer progression and metastases. However, the function of IL-22 in osteosarcoma (OS) remains unclear.Material/MethodsIn this study, the expression of IL-22 in the OS cell line was detected by qRT-PCR. The role of IL-22 in proliferation and invasion in OS cells was tested by MTT and Transwell assays. The protein expression of STAT3, phospho-STAT3, AKT, and phospho-AKT was detected by Western blot analysis.ResultsThe results showed that IL-22 was upregulated in OS cells. IL-22 dose-independently promoted OS cells proliferation and invasion, which could be reversed by IL-22 antibody or STAT3 siRNA. Furthermore, IL-22 exposure of OS cells resulted in dose-independently increased levels of phosphorylated STAT3 protein kinases. Interestingly, IL-22 did not influence the expression of phosphorylated AKT.ConclusionsThese results suggest that IL-22 promotes OS cells proliferation and invasion and its effect is mediated by activation of the STAT3 pathway. These findings demonstrate that IL-22 may serve as a promising molecular biomarker for diagnosis and therapy for OS patients.

Interleukin‑22 modulates cisplatin sensitivity of osteosarcoma cells by regulating the STAT3 signaling pathway

“…IL-22 has been reported to activate the STAT3 signaling pathway in cells and initiate downstream transduction signals (28)(29)(30), including in osteosarcoma cells (10). Therefore, the present investigated the effect of IL-22 expression on the STAT3 signaling pathway in DDP-treated osteosarcoma cells.…”

“…Evidence shows that elevated levels of IL-22 in several malignancies is detrimental (15-18). In the present study, the study (10). The ability of IL-22 to regulate the sensitivity of osteosarcoma cells to cisplatin and its molecular mechanism was also investigated.…”

“…It encodes an α helix protein with a structure that is ~23% homologous to IL-10 and belongs to the IL-10 family (9). A previous study has shown that IL-22 may regulate the growth of osteosarcoma cells (10). However, whether IL-22 regulates cisplatin sensitivity in osteosarcoma cells remains unclear.…”

Interleukin-22 Mediates the Chemotactic Migration of Breast Cancer Cells and Macrophage Infiltration of the Bone Microenvironment by Potentiating S1P/SIPR Signaling

“…IL-22 has been suggested to regulate the progression of several tumors [10][11][12] but its involvement in breast cancer metastasis is largely unknown. To determine the potential involvement of elevated IL-22R1 and S1PR1 expression in breast cancer metastasis to distant organs, we analyzed a cohort of 65 breast cancer patients harboring a metastasis at a non-mineral site (lung and liver), brain, or bone.…”

“…Interleukin-22 (IL-22) is a key effector cytokine that plays a role in the pathogenesis of several inflammatory diseases including cancer [9]. Several lines of evidence have suggested that IL-22 signaling may regulate tumor progression by promoting cell growth and survival [10][11][12]. In further support of this, the aberrant expression of the IL-22 cognate receptor, interleukin-22 receptor 1 (IL-22R1), has been observed in many types of tumor, including lymphomas [13] and pancreatic [14], lung [15], and colon cancers [16].…”