BackgroundBoth tumor-associated macrophages (TAMs) and the epithelial to mesenchymal transition (EMT) of cancer cells play key roles in promoting tumor progression. However, whether TAMs could induce EMT in the progression of oral squamous cell carcinoma (OSCC) remains undefined.ResultsHere we detected the expression of macrophages markers CD68 and CD163, epithelial marker E-cadherin and mesenchymal marker vimentin in 127 OSCC patients by using semi-quantitative immunohistochemistry. CD68 and CD163 expression was not confined to the infiltrating TAMs, but also detected in cancer cells. The high number of CD68-positive macrophages was correlated with poor overall survival. Meanwhile, the expression of CD163 both in macrophages and in cancer cells was associated with poor overall survival and had a significant prognostic impact in OSCC. Importantly, the expression of CD163 in cancer cells had a significant relationship with E-cadherin and vimentin. Furthermore, the incubation of TAMs conditioned medium resulted in a fibroblast-like appearance of cancer cells (HN4, HN6 and SCC9) together with the decreased/increased expression of E-cadherin/ vimentin, which were correlated with the enhanced ability of migration and invasion.ConclusionsOur results indicate that TAMs could promote the EMT of cancer cells, thereby leading to the progression of oral cancer.
Insulin-like growth factor 1 (IGF-1) plays an important role in the regulation of tooth root development, and stem cells from apical papilla (SCAPs) are responsible for the formation of root pulp and dentin. To date, it remains unclear whether IGF-1 can regulate the function of SCAPs. In this study, SCAPs were isolated and purified from human immature root apex, and stimulated by 100 ng/mL exogenous IGF-1. The effects of IGF-1 on the proliferation and differentiation of SCAPs were subsequently investigated. IGF-1 treated SCAPs presented the morphological and ultrastructural changes. Cell proliferation, alkaline phosphatase (ALP) activity and mineralization capacity of SCAPs were increased by IGF-1. Western blot and quantitative RT-PCR analyses further demonstrated that the expression of osteogenic-related proteins and genes (e.g., alkaline phosphatase, runt-related transcription factor 2, osterix, and osteocalcin) was significantly up-regulated in IGF-1 treated SCAPs, whereas the expression of odontoblast-specific markers (e.g., dentin sialoprotein and dentin sialophosphoprotein) was down-regulated by IGF-1. In vivo results revealed that IGF-1 treated SCAPs mostly gave birth to bone-like tissues while untreated SCAPs mainly generated dentin-pulp complex-like structures after transplantation. The present study revealed that IGF-1 can promote the osteogenic differentiation and osteogenesis capacity of SCAPs, but weaken their odontogenic differentiation and dentinogenesis capability, indicating that IGF-1 treated SCAPs can be used as a potential candidate for bone tissue engineering.
IntroductionEstrogen plays an important role in the osteogenic differentiation of mesenchymal stem cells, while stem cells from apical papilla (SCAP) can contribute to the formation of dentin/bone-like tissues. To date, the effects of estrogen on the differentiation of SCAP remain unclear.MethodsSCAP was isolated and treated with 10-7 M 17beta-estradiol (E2). The odonto/osteogenic potency and the involvement of mitogen-activated protein kinase (MAPK) signaling pathway were subsequently investigated by using methyl-thiazolyl-tetrazolium (MTT) assay, and other methods.ResultsMTT and flow cytometry results demonstrated that E2 treatment had no effect on the proliferation of SCAP in vitro, while alkaline phosphatase (ALP) assay and alizarin red staining showed that E2 can significantly promote ALP activity and mineralization ability in SCAP. Real-time reverse transcription polymerase chain reaction (RT-PCR) and western blot assay revealed that the odonto/osteogenic markers (ALP, DMP1/DMP1, DSPP/DSP, RUNX2/RUNX2, OSX/OSX and OCN/OCN) were significantly upregulated in E2-treated SCAP. In addition, the expression of phosphor-p38 and phosphor-JNK in these stem cells was enhanced by E2 treatment, as was the expression of the nuclear downstream transcription factors including phosphor-Sp1, phosphor-Elk-1, phosphor-c-Jun and phosphor-c-Fos, indicating the activation of MAPK signaling pathway during the odonto/osteogenic differentiation of E2-treated SCAP. Conversely, the differentiation of E2-treated SCAP was inhibited in the presence of MAPK specific inhibitors.ConclusionsThe ondonto/osteogenic differentiation of SCAP is enhanced by 10-7 M 17beta-estradiol via the activation of MAPK signaling pathway.
Periodontitis is a chronic inflammatory disease induced by bacteria. Exposure of the host to periodontal pathogens and their virulence factors induces a hyporesponsive state to subsequent challenge, which is termed endotoxin tolerance. In this experiment, we studied the cytokine production in THP-1 cells upon single or repeated Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) or Escherichia coli (E. coli) LPS stimulation by ELISA. In addition, the protein expression profiles of Toll-like receptor 2 (TLR2), TLR4, IL-1 receptor-associated kinase 4 (IRAK4) and IRAK-M and the gene expression changes of Toll-interacting protein (Tollip) and suppressor of cytokine-signaling-1 (SOCS1) were explored to identify possible mechanisms for changes in cytokine secretion. After repeated stimulation with P. gingivalis LPS or E. coli LPS, secretions of TNF-α and IL-1β were decreased significantly compared with those following single challenge, while the levels of IL-10 were increased (p < 0.05). Only comparable levels of IL-8 were confirmed in P. gingivalis LPS-tolerized cells (p > 0.05). In addition, severe downregulation of TLR2 was detected in THP-1 cells retreated with P. gingivalis LPS, and the reduction of TLR4 expression was observed in cells restimulated with E. coli LPS (p < 0.05). Precondition with P. gingivalis LPS or E. coli LPS also led to an enhancement of IRAK-M and SOCS1, while maintaining the expressions of IRAK4 and Tollip. This pattern of cytokine production indicates the different effects of endotoxin tolerance triggered by P. gingivalis LPS and E. coli LPS, which might contribute to limiting inflammatory damage. Moreover, TLR2, TLR4, IRAK-M, and SOCS1 might play important roles in developing tolerance.
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