INT231983

Context Info Confidence 0.72 First Reported 2008 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 9 Total Number 10 Disease Relevance 7.44 Pain Relevance 0.40

Anatomy Link Frequency fibroblast 2 bladder 2 endothelial cells 1 cleavage 1 annulus 1 Tsp1 (Mus musculus)

Pain Link Frequency Relevance Heat metalloproteinase 13 99.46 Inflammation 84 93.44 agonist 16 63.12 addiction 5 50.00 tolerance 6 48.44 cytokine 12 31.36 chemokine 5 22.28 imagery 30 5.00 isoflurane 10 5.00 anesthesia 4 5.00

Disease Link Frequency Relevance Heat Bladder Cancer 364 99.00 Cancer 658 97.04 Prostate Cancer 50 95.88 Targeted Disruption 64 95.12 INFLAMMATION 84 93.44 Reprotox - General 1 32 90.00 Cleidocranial Dysplasia 10 88.20 Hyperplasia 10 86.96 Apoptosis 32 82.36 Metastasis 25 80.24

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TSP1 is involved in the formation and resolution of a fibrin clot and binds to many proteins and proteases.(16) TSP1 interacts with heparan sulfates, proteoglycans, integrins, fibrinogen and fibronectin.(18) It also binds to components of the fibrinolytic system (plasminogen, urokinase and its inhibitor PAI-1)(19,20) and to cathepsin G and elastase.(21)

Localization (involved) of TSP1

1) Confidence 0.72 Published 2008 Journal Biomarker Insights Section Body Doc Link PMC2600574 Disease Relevance 0.44 Pain Relevance 0.09

The data suggest that down-regulation of TSP1 secretion in bladder is important in facilitating this switch.

Localization (secretion) of TSP1 in bladder

2) Confidence 0.69 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.94 Pain Relevance 0

granules [15,16], but TSP1 is now also known to be secreted by a variety of different cells including vascular smooth muscle [17], fibroblasts [18], and endothelial cells [19,20].

Localization (secreted) of TSP1 in endothelial cells

3) Confidence 0.69 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.63 Pain Relevance 0.03

Thrombospondin-1 (TSP1) is a secreted protein that forms a 450-kDa homotrimer.

Localization (secreted) of TSP1

4) Confidence 0.69 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.78 Pain Relevance 0.03

Although the grade of leukocyte infiltration was similar among the genotypes by the end of the study, higher levels of both, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were secreted by TSP1?

Localization (secreted) of TSP1 in fibroblast

5) Confidence 0.68 Published 2008 Journal Biomarker Insights Section Body Doc Link PMC2600574 Disease Relevance 1.22 Pain Relevance 0.12

Secreted TSP1 was found to be expressed in the bladder stroma of all animals, but TSP1 expression in the urothelium was greater in castrated animals when compared to intact animals (Figure 6).

Localization (Secreted) of TSP1 in bladder

6) Confidence 0.65 Published 2008 Journal BMC Urol Section Body Doc Link PMC2374790 Disease Relevance 0.54 Pain Relevance 0

ADAMTS1 has previously been reported to regulate angiogenesis by cleaving TSP1, which results in the release of TSP1 from ECM and thereby to decreased angiogenesis [9].

Localization (release) of TSP1

7) Confidence 0.61 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2894797 Disease Relevance 1.01 Pain Relevance 0

In addition, the metalloproteinase domain has the ability to release anti-angiogenic fragments through cleavage of matrix-bound TSP1 and -2 [9].

Localization (release) of TSP1 in cleavage associated with metalloproteinase

8) Confidence 0.57 Published 2010 Journal BMC Cancer Section Body Doc Link PMC2894797 Disease Relevance 0.79 Pain Relevance 0.13

In the mouse disc, TSP-1 was located in some, but not all, cells in annulus tissue from both WT mice (Figure 2a) and TSP-2-null mice (Figure 2b).

Localization (located) of TSP-1 in annulus

9) Confidence 0.44 Published 2008 Journal Arthritis Res Ther Section Body Doc Link PMC2575610 Disease Relevance 0 Pain Relevance 0

Three molecules that are vital to the pathophysiological extracellular matrix (ECM) structure, Tn-C, Tsp-1 and SL-1, are secreted by fibroblast-like cells and modulate the structural architecture of the tumor.

Localization (secreted) of Tsp-1 in fibroblast associated with cancer

10) Confidence 0.14 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2661372 Disease Relevance 1.08 Pain Relevance 0

General Comments

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