It is well established that the secretion of thrombospondin-1 (TSP-1) by activated stromal cells and its accumulation in the tumor microenvironment during dysplasia inhibits primary tumor growth ...through inhibition of angiogenesis. This inhibitory function of TSP-1 is actuated either by inhibiting MMP9 activation and the release of VEGF from extracellular matrix or by an interaction with CD36 on the surface of endothelial cells resulting in an increase in apoptosis. In contrast, several published articles have also shown that as tumor cells become more invasive and enter the early stage of carcinoma, they up-regulate TSP-1 expression, which may promote invasion and migration. In our
studies using the polyoma middle T antigen (PyT) transgenic mouse model of breast cancer, we observed that the absence of TSP-1 significantly increased the growth of primary tumors, but delayed metastasis to the lungs. In this study, we propose a mechanism for the promigratory function of TSP-1 in mouse mammary tumor cells
. We demonstrate the correlations between expression of TSP-1 and its receptor integrin α3β1, which is considered a promigratory protein in cancer cells. In addition we propose that binding of TSP-1 to integrin α3β1 is important for mediating actin filament polymerization and therefore, cell motility. These findings can help explain the dual functionality of TSP-1 in cancer progression.
Debris discs are evidence of the ongoing destructive collisions between planetesimals, and their presence around stars also suggests that planets exist in these systems. In this paper, we present ...submillimetre images of the thermal emission from debris discs that formed the SCUBA-2 Observations of Nearby Stars (SONS) survey, one of seven legacy surveys undertaken on the James Clerk Maxwell telescope between 2012 and 2015. The overall results of the survey are presented in the form of 850 microns (and 450 microns, where possible) images and fluxes for the observed fields. Excess thermal emission, over that expected from the stellar photosphere, is detected around 49 stars out of the 100 observed fields. The discs are characterised in terms of their flux density, size (radial distribution of the dust) and derived dust properties from their spectral energy distributions. The results show discs over a range of sizes, typically 1-10 times the diameter of the Edgeworth-Kuiper Belt in our Solar System. The mass of a disc, for particles up to a few millimetres in size, is uniquely obtainable with submillimetre observations and this quantity is presented as a function of the host stars' age, showing a tentative decline in mass with age. Having doubled the number of imaged discs at submillimetre wavelengths from ground-based, single dish telescope observations, one of the key legacy products from the SONS survey is to provide a comprehensive target list to observe at high angular resolution using submillimetre/millimetre interferometers (e.g., ALMA, SMA).
Thrombospondin is an adhesive glycoprotein that supports cell attachment, spreading, and migration. The murine thrombospondin gene is approximately 18 kb in length and includes 22 exons. ...Interspecific backcross analysis using progeny derived from matings of (C57BL/6J x Mus spretus) F1 x C57BL/6J mice indicates that the thrombospondin gene is tightly linked to the Fshb, Actcl, Ltk, and B2M loci on murine chromosome 2. The sequence of the murine gene is very similar to that of the human gene in (1) regions of the promoter, (2) the coding region, and (3) the 3'-untranslated region. The predicted amino acid sequence of the mature murine thrombospondin subunit is 95.1% identical to that of the human. The sequences of these two species are most similar at the regions containing the type 1, 2, and 3 repeats as well as the COOH-terminal globular domain. The thrombospondin promoter is similar to the 5' flanking region of some housekeeping and growth control genes in that it contains multiple GC-rich regions and lacks a CAAT box. The presence of various consensus sequences suggests that thrombospondin gene expression is regulated by cAMP, cytokines, and steroid hormones.
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