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Background: The role of stress signals in regulating gastric cancer initiation and progression is not quite clear. It is known that stress signals modulate multiple processes such as immune function, cell migration and angiogenesis. However, few studies have investigated the mechanisms of how stress signals contribute to gastric cancer angiogenesis.Methods: Here, we used β2-adrenergic receptor (β2-AR) agonist isoprenaline to imitate a stress signal and demonstrated the molecular mechanism underlying stress's influence on tumor angiogenesis.Results: We found that isoprenaline stimulated vascular endothelial growth factor (VEGF) secretion in gastric cancer cells and plexin-A1 expression was induced by human recombinant VEGF165 in both gastric cancer cells and vascular endothelial cells. Furthermore, interfere with plexin-A1 expression in gastric cancer cells influence HUVEC tube formation, migration and tumor growth in vivo.Conclusions: These findings suggest that isoprenaline stimulate VGEF secretion and subsequently up-regulate the expression of plexin-A1 and VEGFR2 in gastric cancer cells, which form a positive impetus to promote tumor angiogenesis. This study reveals a novel molecular mechanism that a stress signal like isoprenaline may enhance angiogenesis via activating plexin-A1/VEGFR2 signaling pathway in gastric cancer, which may be a potential target in development of an anti-angiogenic therapy for gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract: Recognizing juvenile and relict lithospheric mantle is crucial in unraveling the mechanism of lithospheric thinning (delamination vs. thermal/mechanic erosion). The H2O contents and Sr–Nd isotopic compositions of juvenile lithospheric mantle are expected to be similar to the MORB source (asthenospheric mantle), whereas those of the relict lithospheric mantle should be of typical cratonic character. Consequently, combined analysis of H2O contents and Sr–Nd isotope compositions could be an effective way to distinguish the juvenile and relict lithospheric mantle. Among the peridotite minerals, clinopyroxene is the major host for rare earth elements as well as H2O contents, making it the most suitable target sample for such analyses. We collected fresh peridotite xenoliths hosted by Cenozoic basalts from Beiyan, Shandong province and Yangyuan, Hebei province to carry out combined analyses of major elements, trace elements, Sr–Nd isotopes and H2O contents for clinopyroxene. At both Beiyan and Yangyuan, pyroxene from peridotite xenoliths shows homogenous H2O contents within individual grains, and equilibrium distribution of H2O contents between clinopyroxene and orthopyroxene has been achieved. There is a positive correlation between H2O contents and Al contents in clinopyroxene and orthopyroxene, these features imply that the pyroxenes largely preserve the H2O contents of their mantle source. The variations of H2O contents in clinopyroxene are controlled by partial melting rather than the later episode of mantle metasomatism, because there is a correlation between H2O contents of clinopyroxene and degree of partial melting index (Yb content of clinopyroxene and Mg# of olivine). Based on the correlation between H2O contents and Sr isotope ratios of clinopyroxene, the estimated H2O contents and 87Sr/86Sr ratios of mantle source of peridotites in Beiyan (450 to less than 600ppm, and ~0.7028 respectively) are similar to the MORB source, thereby implying that the lithospheric mantle beneath Beiyan is juvenile. In contrast, the variation of H2O contents and Sr–Nd isotope compositions of clinopyroxene from the Yangyuan peridotites is best explained as relict mantle (H2O contents less than 300ppm and EM1-type Sr–Nd isotope ratios) coexisting with juvenile lithospheric mantle (H2O contents more than 600ppm and 87Sr/86Sr about 0.7030). These conclusions are in agreement with previous studies which have demonstrated that the lithospheric mantle beneath Beiyan is made up of juvenile material accreted from the asthenosphere after the North China Craton had undergone thinning. [Copyright &y& Elsevier]