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Sökning: onr:"swepub:oai:DiVA.org:umu-40763" > Thrombospondin-1 re...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00004037naa a2200457 4500
001oai:DiVA.org:umu-40763
003SwePub
008110309s2010 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-407632 URI
0247 a https://doi.org/10.1038/labinvest.2010.902 DOI
040 a (SwePub)umu
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Fitchev, Philip P4 aut
2451 0a Thrombospondin-1 regulates the normal prostate in vivo through angiogenesis and TGF-beta activation
264 1b Elsevier BV,c 2010
338 a print2 rdacarrier
520 a Castration experiments in rodents show that the stromal vasculature is critical to the androgen-mediated prostate growth regulation. However, the role of angiogenesis inhibitors, such as thrombospondin-1 (TSP-1), in this process is unclear. TSP-1 is a multifunctional glycoprotein that can function as a potent angiogenesis inhibitor and an in vivo activator of latent transforming growth factor-beta (TGF-beta) in some tissues. On the basis of these observations, we hypothesized that TSP-1 regulated androgen withdrawal-induced prostate regression and that this process was mediated not only through antiangiogenic activity but also through TGF-beta activation. To test this, we evaluated angiogenic activity in human prostate epithelial and stromal cells treated with androgens and hypoxia in vitro. TSP-1 knockout mice were characterized to investigate the in vivo functions of TSP-1. In vitro, we found that androgens and hypoxia differentially regulated TSP-1 and angiogenic activity. Androgens stimulated normal epithelial cell, but inhibited normal stromal cell, angiogenic activity. Conversely, hypoxia stimulated stromal while inhibiting epithelial activity. Thus, in vivo, net angiogenic activity must reflect cellular interactions. And, we found that media conditioned by epithelial cells grown under normoxic conditions stimulated stromal cell angiogenic activity, and if epithelial cells were grown under hypoxic conditions, stromal activity was further increased. TSP-1 levels, however, were unchanged. In vivo, TSP-1 loss in a mouse model led to prostate epithelial hyperplasia by 3 months of age with only a modest stromal effect. Androgens suppressed TSP-1 as expression increased after castration both in normal mouse prostate and in human prostate cancer tissues. In addition, TSP-1 expression corresponded to increased TGF-beta activation in mouse tissues, specifically in the stromal compartment. These data show a critical role for TSP-1 in prostate epithelial and stromal growth regulation through angiogenic inhibition and activation of latent TGF-beta. Therefore, loss of TSP-1 during tumorigenesis would eliminate two barriers to cancer progression.
650 7a LANTBRUKSVETENSKAPERx Veterinärmedicinx Patobiologi0 (SwePub)403022 hsv//swe
650 7a AGRICULTURAL SCIENCESx Veterinary Sciencex Pathobiology0 (SwePub)403022 hsv//eng
653 a angiogenesis; cancer; prostate; thrombospondin-1; transforming growth factor-β; vascular endothelial growth factor
653 a Pathology
653 a Patologi
653 a Pathology
653 a patologi
7001 a Wcislak, Susan M4 aut
7001 a Lee, Chung4 aut
7001 a Bergh, Andersu Umeå universitet,Patologi4 aut0 (Swepub:umu)anbe0010
7001 a Brendler, Charles B4 aut
7001 a Stellmach, Veronica M4 aut
7001 a Crawford, Susan E4 aut
7001 a Mavroudis, Constantine D4 aut
7001 a Cornwell, Mona L4 aut
7001 a Doll, Jennifer A4 aut
7102 a Umeå universitetb Patologi4 org
7730 t Laboratory Investigationd : Elsevier BVg 90:7, s. 1078-1090q 90:7<1078-1090x 0023-6837x 1530-0307
8564 u https://www.nature.com/articles/labinvest201090.pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-40763
8564 8u https://doi.org/10.1038/labinvest.2010.90

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