IL-6 and CXCL8 mediate osteosarcoma-lung interactions critical to metastasis.

Osteosarcoma (OS), a malignant tumor of bone, kills through aggressive metastatic spread almost exclusively to the lung. Mechanisms driving this tropism for lung tissue remain unknown, though likely invoke specific interactions between tumor cells and other cells within the lung metastatic niche. Aberrant overexpression of ΔNp63 in OS cells directly drives production of IL-6 and CXCL8. All these factors were expressed at higher levels in OS lung metastases than in matched primary tumors from the same patients. Expression in cell lines correlated strongly with lung colonization efficiency in murine xenograft models. Lentivirus-mediated expression endowed poorly metastatic OS cells with increased metastatic capacity. Disruption of IL-6 and CXCL8 signaling using genetic or pharmaceutical inhibitors had minimal effects on tumor cell proliferation in vitro or in vivo, but combination treatment inhibited metastasis across multiple models of metastatic OS. Strong interactions occurred between OS cells and both primary bronchial epithelial cells and bronchial smooth muscle cells that drove feed-forward amplification of IL-6 and CXCL8 production. These results identify IL-6 and CXCL8 as primary mediators of OS lung tropism and suggest pleiotropic, redundant mechanisms by which they might effect metastasis. Combination therapy studies demonstrate proof of concept for targeting these tumor-lung interactions to affect metastatic disease.

Sum-frequency spectroscopy of a monolayer of zinc arachidate at the solid-solid interface.

Infrared-visible sum-frequency spectroscopy has been used to record the vibrational spectrum of a zinc arachidate monolayer at the interface between a sapphire prism and a fused silica lens. Spectra have been recorded for the monolayer deposited on the prism before, during, and after contact, and as a function of increasing pressure. Sum-frequency spectra are reported of the monolayer under sliding contact. The monolayer is found to be resistant to pressure- and shear-induced conformational disorder. However, frequency shifts, drops in peak intensities, and changes in peak intensity ratios have been observed as the monolayer is placed in contact between the prism and the lens. Transfer of monolayer material between the two surfaces is observed and is confirmed by spectra obtained with a monolayer deposited on the surface of the lens rather than the prism. On one face of the sapphire prism, the monolayer reconstructs to a low symmetry layer, probably due to epitaxy. The epitaxial structure disappeared in contact. Existing models for calculating sum-frequency spectra have been extended to include unit cells containing two molecules and torsion about the terminal C-C bond. This model can explain some, but not all, of the experimental observations.

Ag@Au Concave Cuboctahedra: A Unique Probe for Monitoring Au-Catalyzed Reduction and Oxidation Reactions by Surface-Enhanced Raman Spectroscopy.

We report a facile synthesis of Ag@Au concave cuboctahedra by titrating aqueous HAuCl4 into a suspension of Ag cuboctahedra in the presence of ascorbic acid (AA), NaOH, and poly(vinylpyrrolidone) (PVP) at room temperature. Initially, the Au atoms derived from the reduction of Au(3+) by AA are conformally deposited on the entire surface of a Ag cuboctahedron. Upon the formation of a complete Au shell, however, the subsequently formed Au atoms are preferentially deposited onto the Au{100} facets, resulting in the formation of a Ag@Au cuboctahedron with concave structures at the sites of {111} facets. The concave cuboctahedra embrace excellent SERS activity that is more than 70-fold stronger than that of the original Ag cuboctahedra at an excitation wavelength of 785 nm. The concave cuboctahedra also exhibit remarkable stability in the presence of an oxidant such as H2O2 because of the protection by a complete Au shell. These two unique attributes enable in situ SERS monitoring of the reduction of 4-nitrothiophenol (4-NTP) to 4-aminothiophenol (4-ATP) by NaBH4 through a 4,4'-dimercaptoazobenzene (trans-DMAB) intermediate and the subsequent oxidation of 4-ATP back to trans-DMAB upon the introduction of H2O2.