ADAMTS1 alters blood vessel morphology and TSP1 levels in LNCaP and LNCaP-19 prostate tumors

<p>Abstract</p> <p>Background</p> <p>Decreased expression of the angiogenesis inhibitor ADAMTS1 (ADAM metallopeptidase with thrombospondin type 1 motif, 1) has previously been reported during prostate cancer progression. The aim of this study was to investigate the function of ADAMTS1 in prostate tumors.</p> <p>Methods</p> <p>ADAMTS1 was downregulated by shRNA technology in the human prostate cancer cell line LNCaP (androgen-dependent), originally expressing ADAMTS1, and was upregulated by transfection in its subline LNCaP-19 (androgen-independent), expressing low levels of ADAMTS1. Cells were implanted subcutaneously in nude mice and tumor growth, microvessel density (MVD), blood vessel morphology, pericyte coverage and thrombospondin 1 (TSP1) were studied in the tumor xenografts.</p> <p>Results</p> <p>Modified expression of ADAMTS1 resulted in altered blood vessel morphology in the tumors. Low expression levels of ADAMTS1 were associated with small diameter blood vessels both in LNCaP and LNCaP-19 tumors, while high levels of ADAMTS1 were associated with larger vessels. In addition, TSP1 levels in the tumor xenografts were inversely related to ADAMTS1 expression. MVD and pericyte coverage were not affected. Moreover, upregulation of ADAMTS1 inhibited tumor growth of LNCaP-19, as evidenced by delayed tumor establishment. In contrast, downregulation of ADAMTS1 in LNCaP resulted in reduced tumor growth rate.</p> <p>Conclusions</p> <p>The present study demonstrates that ADAMTS1 is an important regulatory factor of angiogenesis and tumor growth in prostate tumors, where modified ADAMTS1 expression resulted in markedly changed blood vessel morphology, possibly related to altered TSP1 levels.</p

A recursive software architecture for location-aware services

Submitted to UbiComp 2002A GLObal Smart Space (GLOSS) provides support for interaction amongst people, artefacts and places while taking account of both context and movement on a global scale. Crucial to the definition of a GLOSS is the provision of a set of services, which we term location-aware services, that detect, convey, store and exploit location information. We first describe a framework (ontology), using a small set of concepts, for defining a GLOSS. This allows different services to be implemented without duplication of the basic mechanisms, and abstracts over specific details of the technologies used, thereby accommodating both heterogeneity and evolution. Secondly, we introduce a set of location-aware metaphors that are defined in terms of the GLOSS concepts. Thirdly, we propose a recursive software architecture to support the implementation of the metaphors within the framework. Finally we outline how the software architecture may be applied recursively to provide scalability for location-aware services in the global context.Postprin

A recursive software architecture for location-aware services

A GLObal Smart Space (GLOSS) provides support for interaction amongst people, artefacts and places while taking account of both context and movement on a global scale. Crucial to the definition of a GLOSS is the provision of a set of services, which we term location-aware services, that detect, convey, store and exploit location information. We first describe a framework (ontology), using a small set of concepts, for defining a GLOSS. This allows different services to be implemented without duplication of the basic mechanisms, and abstracts over specific details of the technologies used, thereby accommodating both heterogeneity and evolution. Secondly, we introduce a set of location-aware metaphors that are defined in terms of the GLOSS concepts. Thirdly, we propose a recursive software architecture to support the implementation of the metaphors within the framework. Finally we outline how the software architecture may be applied recursively to provide scalability for location-aware services in the global context