Genomes and Genes
Summary: An extracellular matrix glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin. Thrombospondin-1 is believed to play a role in cell migration and proliferation, during embryogenesis and wound repair. Also, it has been studied for its use as a potential regulator of tumor growth and metastasis.
- Zhang M, Tao W, Pan S, Sun X, Jiang H. Low-dose metronomic chemotherapy of paclitaxel synergizes with cetuximab to suppress human colon cancer xenografts. Anticancer Drugs. 2009;20:355-63 pubmed publisher..These results suggest that the combination of paclitaxel LDM chemotherapy and cetuximab represents a potent strategy to combat colon cancers. ..
- Turpie B, Yoshimura T, Gulati A, Rios J, Dartt D, Masli S. Sjögren's syndrome-like ocular surface disease in thrombospondin-1 deficient mice. Am J Pathol. 2009;175:1136-47 pubmed publisher..Together, these results indicate that TSP-1 deficiency results in a spontaneous form of chronic dry eye and aberrant histopathology associated with Sjögren's syndrome. ..
- Matsuba M, Hutcheon A, Zieske J. Localization of thrombospondin-1 and myofibroblasts during corneal wound repair. Exp Eye Res. 2011;93:534-40 pubmed publisher..These data are in agreement with our hypothesis that TSP-1 localization in the stromal matrix is involved in the transformation of keratocytes into myofibroblasts. ..
- Donmez G, Sullu Y, Baris S, Yildiz L, Aydin O, Karagoz F, et al. Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), and thrombospondin-1 (TSP-1) expression in urothelial carcinomas. Pathol Res Pract. 2009;205:854-7 pubmed publisher..014, r=-0.21). Increased VEGF and MMP-9 expression as well as decreased TSP-1 expression may play considerable roles in the invasion and differentiation of urothelial carcinoma. ..
- Liu Y, Annis D, Mosher D. Interactions among the epidermal growth factor-like modules of thrombospondin-1. J Biol Chem. 2009;284:22206-12 pubmed publisher..7, which recognize epitopes in E2, bound to E12, E23, or E123 with greater affinity than to E2 alone. These results indicate that interactions among the modules of E123 influence the tertiary structure and calcium binding of E2. ..
- García Díaz D, Arellano A, Milagro F, Moreno Aliaga M, Portillo M, Martinez J, et al. Glucose and insulin modify thrombospondin 1 expression and secretion in primary adipocytes from diet-induced obese rats. J Physiol Biochem. 2011;67:453-61 pubmed publisherb>Thrombospondin 1 (TSP-1), an antiangiogenic factor and transforming growth factor (TGF)-? activity regulator, has been recently recognized as an adipokine that correlates with obesity, inflammation and insulin resistance processes...
- Zhou J, Feng X, Ban B, Liu J, Wang Z, Xiao W. Elongation factor ELL (Eleven-Nineteen Lysine-rich Leukemia) acts as a transcription factor for direct thrombospondin-1 regulation. J Biol Chem. 2009;284:19142-52 pubmed publisher..Given the importance of TSP-1 as an anti-angiogenic protein, our findings may have important ramifications for better understanding cancer. ..
- Soto Pantoja D, Ridnour L, Wink D, Roberts D. Blockade of CD47 increases survival of mice exposed to lethal total body irradiation. Sci Rep. 2013;3:1038 pubmed publisher..Thus, CD47 is a new target for radiomitigation that prevents both hematopoietic and gastrointestinal radiation syndromes. ..
- Bauer P, Bauer E, Rogers N, Yao M, Feijóo Cuaresma M, Pilewski J, et al. Activated CD47 promotes pulmonary arterial hypertension through targeting caveolin-1. Cardiovasc Res. 2012;93:682-93 pubmed publisher..Activated CD47 is upregulated in experimental and human PAH and promotes disease by limiting Cav-1 inhibition of dysregulated eNOS. ..
- Colombo G, Margosio B, Ragona L, Neves M, Bonifacio S, Annis D, et al. Non-peptidic thrombospondin-1 mimics as fibroblast growth factor-2 inhibitors: an integrated strategy for the development of new antiangiogenic compounds. J Biol Chem. 2010;285:8733-42 pubmed publisher..Altogether, this study demonstrates that new biological insights obtained by integrated multidisciplinary approaches can be used to develop small molecule mimics of endogenous proteins as therapeutic agents. ..
- Saban D, Bock F, Chauhan S, Masli S, Dana R. Thrombospondin-1 derived from APCs regulates their capacity for allosensitization. J Immunol. 2010;185:4691-7 pubmed publisher..Future strategies targeting APCs for TSP-1 upregulation may thus be effective in promoting allograft survival. ..
- Kaur S, Martin Manso G, Pendrak M, Garfield S, Isenberg J, Roberts D. Thrombospondin-1 inhibits VEGF receptor-2 signaling by disrupting its association with CD47. J Biol Chem. 2010;285:38923-32 pubmed publisher..These results reveal that anti-angiogenic signaling through CD47 is highly redundant and extends beyond inhibition of nitric oxide signaling to global inhibition of VEGFR2 signaling. ..
- Yang Q, Tian Y, Ostler K, Chlenski A, Guerrero L, Salwen H, et al. Epigenetic alterations differ in phenotypically distinct human neuroblastoma cell lines. BMC Cancer. 2010;10:286 pubmed publisher..Our results suggest that epigenetic aberrations contribute to NB phenotype, and that tumorigenic properties can be inhibited by reversing the epigenetic changes with 5-Aza-dC. ..
- Mittal R, Gonzalez Gomez I, Prasadarao N. Escherichia coli K1 promotes the ligation of CD47 with thrombospondin-1 to prevent the maturation of dendritic cells in the pathogenesis of neonatal meningitis. J Immunol. 2010;185:2998-3006 pubmed publisher..coli significantly upregulates the expression of CD47, an integrin-associated protein, and its natural ligand thrombospondin 1 (TSP-1)...
- Raman P, Harry C, Weber M, Krukovets I, Stenina O. A novel transcriptional mechanism of cell type-specific regulation of vascular gene expression by glucose. Arterioscler Thromb Vasc Biol. 2011;31:634-42 pubmed publisher..Transcriptional response of vascular cells to high glucose is cell type-specific and involves activation of distinct transcription factors, providing a basis for tissue-specific changes of vasculature in diabetics. ..
- Inoue M, Jiang Y, Barnes R, Tokunaga M, Martinez Santibañez G, Geletka L, et al. Thrombospondin 1 mediates high-fat diet-induced muscle fibrosis and insulin resistance in male mice. Endocrinology. 2013;154:4548-59 pubmed publisherb>Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice...
- Shariat S, Youssef R, Gupta A, Chade D, Karakiewicz P, Isbarn H, et al. Association of angiogenesis related markers with bladder cancer outcomes and other molecular markers. J Urol. 2010;183:1744-50 pubmed publisher..Vascular endothelial growth factor, basic fibroblast growth factor and thrombospondin 1 expression data were collected, as were microvessel density data...
- Taraboletti G, Rusnati M, Ragona L, Colombo G. Targeting tumor angiogenesis with TSP-1-based compounds: rational design of antiangiogenic mimetics of endogenous inhibitors. Oncotarget. 2010;1:662-73 pubmed..Pharmacophore-based approaches are thus feasible tools to exploit naturally occurring PPI, by generating a set of lead compounds mimetic of endogenous proteins, as a starting point for the development of novel therapeutic agents. ..
- Bailey Dubose K, Zayzafoon M, Murphy Ullrich J. Thrombospondin-1 inhibits osteogenic differentiation of human mesenchymal stem cells through latent TGF-? activation. Biochem Biophys Res Commun. 2012;422:488-93 pubmed publisher..Anti-TGF-? neutralizing antibody also increased alkaline phosphatase expression in the presence of TSP1. These studies show that TSP1 regulated TGF-? activity is a critical determinant of osteoblast differentiation. ..
- Johnson C, Kleshchenko Y, Ikejiani A, Udoko A, Cardenas T, Pratap S, et al. Thrombospondin-1 interacts with Trypanosoma cruzi surface calreticulin to enhance cellular infection. PLoS ONE. 2012;7:e40614 pubmed publisher..cruzi through the NTSP domain and that this interaction enhances cellular infection. Thus surface TcCRT is a virulent factor that enhances the pathogenesis of T. cruzi infection through TSP-1, which is up-regulated by the parasite. ..
- Tan K, Duquette M, Joachimiak A, Lawler J. The crystal structure of the signature domain of cartilage oligomeric matrix protein: implications for collagen, glycosaminoglycan and integrin binding. FASEB J. 2009;23:2490-501 pubmed publisher..The structure presented here and its unique molecular packing in the crystal identify potential interactive sites for glycosaminoglycans, integrins, and collagens, which are key to cartilage structure and function. ..
- Guo W, Dong Z, He M, Guo Y, Guo J, Chen Z, et al. Aberrant methylation of thrombospondin-1 and its association with reduced expression in gastric cardia adenocarcinoma. J Biomed Biotechnol. 2010;2010:721485 pubmed publisher..Epigenetic silencing of TSP1 gene by promoter hypermethylation may play an important role in GCA. ..
- Kaur S, Kuznetsova S, Pendrak M, Sipes J, Romeo M, Li Z, et al. Heparan sulfate modification of the transmembrane receptor CD47 is necessary for inhibition of T cell receptor signaling by thrombospondin-1. J Biol Chem. 2011;286:14991-5002 pubmed publisher..Therefore, inhibition of T cell receptor signaling by thrombospondin-1 is mediated by CD47 and requires its modification at Ser(64). ..
- Presser L, Haskett A, Waris G. Hepatitis C virus-induced furin and thrombospondin-1 activate TGF-?1: role of TGF-?1 in HCV replication. Virology. 2011;412:284-96 pubmed publisher..Collectively, these observations provide insight into the mechanism of TGF-?1 activation, which likely manifest in liver fibrosis associated with hepatitis C infection. ..
- Smadja D, d Audigier C, Bieche I, Evrard S, Mauge L, Dias J, et al. Thrombospondin-1 is a plasmatic marker of peripheral arterial disease that modulates endothelial progenitor cell angiogenic properties. Arterioscler Thromb Vasc Biol. 2011;31:551-9 pubmed publisher..TSP-1 is a potential biomarker of PAD and ECFC-induced angiogenesis, suggesting that TSP-1 modulation might improve local tissue ischemia in this setting. ( NCT00377897.). ..
- Ramanathan S, Mazzalupo S, Boitano S, Montfort W. Thrombospondin-1 and angiotensin II inhibit soluble guanylyl cyclase through an increase in intracellular calcium concentration. Biochemistry. 2011;50:7787-99 pubmed publisher..Taken together, these data suggest that sGC not only lowers [Ca(2+)](i) in response to NO, inducing vasodilation, but also is inhibited by high [Ca(2+)](i), providing a fine balance between signals for vasodilation and vasoconstriction. ..
- Firlej V, Mathieu J, Gilbert C, Lemonnier L, Nakhlé J, Gallou Kabani C, et al. Thrombospondin-1 triggers cell migration and development of advanced prostate tumors. Cancer Res. 2011;71:7649-58 pubmed publisher..Here, we reevaluated the role of the endogenous antiangiogenic thrombospondin 1 (TSP1) in prostate carcinomas in which angiogenesis is an active process...
- Liu Y, Mosher D. Interactions among stalk modules of thrombospondin-1. J Biol Chem. 2009;284:28563-70 pubmed publisher..These results indicate that the TSR and thrombospondin-type EGF-like stalk modules act as a unit that may relay conformational information between the N-terminal and C-terminal parts of the protein. ..
- Isenberg J, Qin Y, Maxhimer J, Sipes J, Despres D, Schnermann J, et al. Thrombospondin-1 and CD47 regulate blood pressure and cardiac responses to vasoactive stress. Matrix Biol. 2009;28:110-9 pubmed publisher..Thus, the matricellular protein thrombospondin-1 and its receptor CD47 serve as acute physiological regulators of blood pressure and exert a vasopressor activity to maintain global hemodynamics under stress. ..
- Lee S, Ghosh S, Han H, Stone R, Bottsford Miller J, Shen D, et al. Metronomic activity of CD44-targeted hyaluronic acid-paclitaxel in ovarian carcinoma. Clin Cancer Res. 2012;18:4114-21 pubmed publisher..This study showed that MET HA-TXL regimens have substantial antitumor activity in ovarian carcinoma, likely via a predominant antiangiogenic mechanism. ..
- Gelse K, Klinger P, Koch M, Surmann Schmitt C, von der Mark K, Swoboda B, et al. Thrombospondin-1 prevents excessive ossification in cartilage repair tissue induced by osteogenic protein-1. Tissue Eng Part A. 2011;17:2101-12 pubmed publisher..While OP-1 induces chondrogenesis of the ingrowing cells, TSP-1 prevents their further hypertrophic differentiation and prevents excessive endochondral ossification within the lesions. ..
- Park E, Choi J, Park J, Lee M, Park H, Jung S. Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model. Int J Mol Med. 2009;24:401-7 pubmed..Furthermore, these genes are promising targets for developing biomarkers for monitoring disease progression and therapeutic efficacy in patients with Fabry disease. ..
- Nakao T, Kurita N, Komatsu M, Yoshikawa K, Iwata T, Utsunomiya T, et al. Expression of thrombospondin-1 and Ski are prognostic factors in advanced gastric cancer. Int J Clin Oncol. 2011;16:145-52 pubmed publisher..This study also shows that Ski inhibits the prolonged effects of TGF-? for survival in advanced gastric cancer. ..
- Wei W, Kong B, Yang Q, Qu X. Hepatocyte growth factor enhances ovarian cancer cell invasion through downregulation of thrombospondin-1. Cancer Biol Ther. 2010;9:79-87 pubmed..This study enhances our understanding of the mechanisms of signaling transduction in the HGF-induced invasion and progression of ovarian cancer. ..
- Lee Y, Koch M, Karl D, Torres Collado A, Fernando N, Rothrock C, et al. Variable inhibition of thrombospondin 1 against liver and lung metastases through differential activation of metalloproteinase ADAMTS1. Cancer Res. 2010;70:948-56 pubmed publisher..Tumor angiogenesis is restrained by a variety of endogenous inhibitors, including thrombospondin 1 (TSP1)...
- Malek M, Olfert I. Global deletion of thrombospondin-1 increases cardiac and skeletal muscle capillarity and exercise capacity in mice. Exp Physiol. 2009;94:749-60 pubmed publisher..The increased capillarity alone was sufficient to increase (P < 0.05) exercise capacity. These data demonstrate that the capillary-to-muscle interface is a critical factor that limits oxygen transport during exercise. ..
- Wang S, Gottlieb J, Sorenson C, Sheibani N. Modulation of thrombospondin 1 and pigment epithelium-derived factor levels in vitreous fluid of patients with diabetes. Arch Ophthalmol. 2009;127:507-13 pubmed publisherTo determine the levels of 2 endogenous inhibitors of angiogenesis, thrombospondin 1 (TSP-1) and pigment epithelium-derived factor (PEDF), in the vitreous fluid from patients with and without diabetes...
- Li Y, Tong X, Rumala C, Clemons K, Wang S. Thrombospondin1 deficiency reduces obesity-associated inflammation and improves insulin sensitivity in a diet-induced obese mouse model. PLoS ONE. 2011;6:e26656 pubmed publisher..b>Thrombospondin 1 (TSP1) is a multifunctional extracellular matrix protein that is up-regulated in inflamed adipose tissue...
- Olerud J, Mokhtari D, Johansson M, Christoffersson G, Lawler J, Welsh N, et al. Thrombospondin-1: an islet endothelial cell signal of importance for ?-cell function. Diabetes. 2011;60:1946-54 pubmed publisher..Thus, endothelial-derived TSP-1 activates islet TGF?-1 of importance for ?-cells. Our study indicates a novel role for endothelial cells as functional paracrine support for pancreatic ?-cells. ..
- Ren B, Hale J, Srikanthan S, Silverstein R. Lysophosphatidic acid suppresses endothelial cell CD36 expression and promotes angiogenesis via a PKD-1-dependent signaling pathway. Blood. 2011;117:6036-45 pubmed publisher..Our data thus indicate that the proangiogenic mechanism of LPA may in part be via switching off the antiangiogenic switch mediated by TSR proteins and CD36. ..
- Xie X, Li F, Liu H, Deng Y, Li Z, Fan J. LSKL, a peptide antagonist of thrombospondin-1, attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction. Arch Pharm Res. 2010;33:275-84 pubmed publisher..As TSP-1 is the major activator of TGF-beta1, we demonstrate that LSKL can attenuate renal interstitial fibrosis in vivo by preventing TSP-1-mediated TGF-beta1 activation...
- Aurora A, Aurora A, Biyashev D, Mirochnik Y, Zaichuk T, Sánchez Martinez C, et al. NF-kappaB balances vascular regression and angiogenesis via chromatin remodeling and NFAT displacement. Blood. 2010;116:475-84 pubmed publisher..Our study defines an interactive transcriptional network underlying angiogenic balance and points to HDACi as tools to manipulate the angiogenic switch. ..
- Jiang H, Tao W, Zhang M, Pan S, Kanwar J, Sun X. Low-dose metronomic paclitaxel chemotherapy suppresses breast tumors and metastases in mice. Cancer Invest. 2010;28:74-84 pubmed publisher..The results support the application of paclitaxel LDM therapy to treat advanced breast cancer. ..
- De Luna N, Gallardo E, Sonnet C, Chazaud B, Dominguez Perles R, Suarez Calvet X, et al. Role of thrombospondin 1 in macrophage inflammation in dysferlin myopathy. J Neuropathol Exp Neurol. 2010;69:643-53 pubmed publisher..001). Messenger RNA microarray analysis showed a 3.2-fold increase of thrombospondin 1 (TSP-1) expression in dysferlin-deficient myotubes...
- Zhou L, Picard D, Ra Y, Li M, Northcott P, Hu Y, et al. Silencing of thrombospondin-1 is critical for myc-induced metastatic phenotypes in medulloblastoma. Cancer Res. 2010;70:8199-210 pubmed publisher..These findings indicate the Myc-regulatory network targets Tsp-1 via multiple mechanisms in medulloblastoma transformation, and highlight a novel critical role for Tsp-1 in Myc-mediated aggressive medulloblastoma phenotypes...
- Xu J, Xiao N, Xia J. Thrombospondin 1 accelerates synaptogenesis in hippocampal neurons through neuroligin 1. Nat Neurosci. 2010;13:22-4 pubmed publisherIn cultured rat hippocampal neurons, we found that thrombospondin 1 (TSP1) increased the speed of synapse formation in young neurons, but not the final density of synapses in mature neurons...
- Maier K, Sadowitz B, Cullen S, Han X, Gahtan V. Thrombospondin-1-induced vascular smooth muscle cell migration is dependent on the hyaluronic acid receptor CD44. Am J Surg. 2009;198:664-9 pubmed publisher..TSP-1 and HyA activate the EGFR. TSP-1- and HYA-induced migration share some of the same signaling pathways and the EGFR/CD44 receptors may be a common link. ..
- Rogers N, Thomson A, Isenberg J. Activation of parenchymal CD47 promotes renal ischemia-reperfusion injury. J Am Soc Nephrol. 2012;23:1538-50 pubmed publisher..Taken together, these data imply that CD47 on parenchymal cells promotes injury after renal ischemia and reperfusion. Therefore, CD47 blockade may have therapeutic potential to prevent or suppress ischemia-reperfusion-mediated damage. ..
- Cursiefen C, Maruyama K, Bock F, Saban D, Sadrai Z, Lawler J, et al. Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes. J Exp Med. 2011;208:1083-92 pubmed publisher..Inhibition of VEGF-C is not detected in the absence or blockade of CD36. These findings suggest that TSP-1, by ligating CD36 on monocytic cells, acts as an endogenous inhibitor of lymphangiogenesis. ..