Mucin 1 promotes salivary gland cancer cell proliferation and metastasis by regulating the epidermal growth factor receptor signaling pathway.

Background/purpose: Salivary gland cancer (SGC) is the common malignant tumor of the head and neck region with poor prognosis. Mucin 1 (MUC1) has been reported to be associated with the development of cancer. However, whether MUC1 contributed to the progression of SGC remains to be explored. Materials and methods: Immunohistochemical analysis was used to explore the expression levels of MUC1 in SGC tissues. Cell proliferation, colony formation, wound healing, transwell, and xenograft assays were performed to examine the effects of MUC1 on SGC in vitro and in vivo. Results: We found that the expression level of MUC1 was significantly upregulated in SGC tissues, and the expression level of MUC1 was significantly correlated with lymph node metastasis and TNM stage of SGC. Further exploration demonstrated that MUC1 knockdown drastically inhibited, while its overexpression promoted, cell growth, colony formation, migration, and invasion abilities of SGC cells in vitro. MUC1 knockdown significantly inhibited tumor growth in vivo, and vice versa. More importantly, we found that MUC1 promotes malignant phenotypes of SGC cells by regulating the epidermal growth factor receptor (EGFR) signaling pathway. Conclusion: Our results revealed that MUC1 promotes the development of SGC by mediating the EGFR signaling pathway, which highlights the potential therapeutic target of MUC1/ EGFR in SGC.

In Situ Release of VEGF Enhances Osteogenesis in 3D Porous Scaffolds Engineered with Osterix-Modified Adipose-Derived Stem Cells.

Adipose-derived stem cells (ADSCs) can differentiate into various cell types and thus have great potential for regenerative medicine. Herein, rat ADSCs were isolated; transduced with lentiviruses expressing Osterix (Osx), a transcriptional factor essential for osteogenesis. Osx overexpression upregulated key osteogenesis-related genes, such as special AT-rich binding protein 2, alkaline phosphatase, osteocalcin, and osteopontin, at both mRNA and protein levels. In addition, mineral nodule formation and alkaline phosphatase activity were enhanced in Osx-overexpressing ADSCs. The expression of dickkopf-related protein 1, a potent Wnt signaling pathway inhibitor, was also increased, whereas that of ß-catenin, an intracellular signal transducer in the Wnt pathway, was decreased. ß-catenin expression was partially recovered by treatment with lithium chloride, a canonical Wnt pathway activator. The Osx-expressing ADSCs were then combined with 3D gelatin-coated porous poly(ɛ-caprolactone) scaffolds with a unique release prolife of entrapped recombinant human vascular endothelial growth factor (VEGF). The controlled release of VEGF promoted osteogenic differentiation capacity in vitro. When the scaffold-ADSC complexes were transplanted into rat calvarial critical-sized defects, more bone formed on the gelatin/VEGF-coated scaffolds than on other scaffold types. Taken together, the results indicate that, Osx-overexpression promotes ADSCs' osteogenesis both in vitro and in vivo, which could be enhanced by release of VEGF.

The overexpressed functional transient receptor potential channel TRPM2 in oral squamous cell carcinoma.

TRPM2, one member of the transient receptor potential (TRP) protein super-family, is a Ca2+-permeable channel that is activated by oxidative stress and confers susceptibility to cell death. In the human tongue specimens of carcinoma and the tongue carcinoma SCC cell lines, we observed the enhanced expression of TRPM2. By means of the whole-cell electrophysiological recording, the ADPR-induced currents mediated by TRPM2 were recorded in cultured SCC9 cells. Moreover, after H2O2 treatment for 24 hours, the apoptotic number of SCC9 cells was significantly increased. However, the selectively knocked-down TRPM2 with the small interfering RNA technique inhibited the survival and migration of the SCC9 cancer cells, which was independent of the p53-p21 pathway, since the expression of p21 was enhanced after TRPM2 knockdown. Furthermore, the sub-cellular localization of TRPM2 was remarkably different between cancerous and non-cancerous cells. A significant amount of the TRPM2 proteins were located in the nuclei in cancer cells. All these data suggest that TRPM2 is essential for the survival and migration of SCC cancer cells and may be a potential target for the selective treatment of tongue cancer.