Thrombospondin-1 is a critical effector of oncosuppressive activity of sst2 somatostatin receptor on pancreatic cancer

The somatostatin receptor subtype 2 (sst2) behaves as a tumor suppressor when expressed and stimulated by its ligand somatostatin in pancreatic cancer. We reveal a mechanism underlying oncosuppressive action of sst2, whereby this inhibitory receptor upregulates the expression of the secreted angioinhibitory factor thrombospondin-1 (TSP-1), as demonstrated in exocrine BxPC-3 and endocrine BON pancreatic cancer cells. The sst2-dependent upregulation of TSP-1 occurs through the inhibition of the PI3K pathway. It depends on transcriptional and translational events, involving a previously undescribed IRES in the 5′-UTR of TSP-1 mRNA. Chick chorioallantoic membrane was used as an in vivo model to demonstrate that TSP-1 is a critical effector of the inhibitory role of sst2 on the neoangiogenesis and oncogenesis induced by pancreatic cancer cells. TSP-1 reduced in vitro tubulogenesis of endothelial cells when grown in conditioned medium from pancreatic cancer cells expressing sst2, as compared to those expressing the control vector. TSP-1 inhibited tumor cell-induced neoangiogenesis by directly sequestering the proangiogenic factor VEGF, and inactivating the angiogenesis initiated by VEGFR2 phosphorylation in endothelial cells. Using human pancreatic tissue-microarrays, the expression of both sst2 and TSP-1 was shown to be correlated during the pancreatic neoplastic program. Both proteins are nearly undetectable in normal exocrine pancreas and in most invasive cancer lesions, but their expression is strikingly upregulated in most preinvasive cancer-adjacent lesions. The upregulation of both sst2 and TSP-1 tumor suppressors may function as an early negative feedback to restrain pancreatic carcinogenesis

Declines in both redundant and trace species characterize the latitudinal diversity gradient in tintinnid ciliates

International audienceThe latitudinal diversity gradient is a well-known biogeographic pattern. However, rarely considered is how a cline in species richness may be reflected in the characteristics of species assemblages. Fewer species may equal fewer distinct ecological types, or declines in redundancy (species functionally similar to one another) or fewer trace species, those occurring in very low concentrations. We focused on tintinnid ciliates of the microzooplankton in which the ciliate cell is housed inside a species-specific lorica or shell. The size of lorica oral aperture, the lorica oral diameter (LOD), is correlated with a preferred prey size and maximum growth rate. Consequently, species of a distinct LOD are distinct in key ecologic characteristics, whereas those of a similar LOD are functionally similar or redundant species. We sampled from East Sea/Sea of Japan to the High Arctic Sea. We determined abundance distributions of biological species and also ecological types by grouping species in LOD size-classes, sets of ecologically similar species. In lower latitudes there are more trace species, more size-classes and the dominant species are accompanied by many apparently ecologically similar species, presumably able to replace the dominant species, at least with regard to the size of prey exploited. Such redundancy appears to decline markedly with latitude in assemblages of tintinnid ciliates. Furthermore, the relatively small species pools of the northern high latitude assemblages suggest a low capacity to adapt to changing conditions