ADAMTS1 is regulated by interleukin-1β, not by hypoxia, in chondrosarcoma

Kalinski, Thomas; Krueger, Sabine; Sel, Saadettin; Werner, Kerstin; Röpke, M.; Roessner, Albert

doi:10.1016/j.humpath.2006.06.012

Cited by 24 publications

(23 citation statements)

References 23 publications

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“…Interleukin-1 has been shown to enhance tumor angiogenesis and blocking of IL1 receptor leads to regression of xenografted IL-1-producing tumors. 45 IL1B might also coordinate expression of some other genes downregulated in VEGF siRNA tumors, like ADAMTS1, 46 which encodes for the disintegrin and metalloproteinase with thrombospondin motifs 1 protein. ADAMTS1 inhibits angiogenesis by blocking VEGF 165 interaction with KDR.…”

Section: Discussionmentioning

confidence: 99%

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Saidi

Javerzat

Bellahcène

et al. 2007

Intl Journal of Cancer

101

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Vascular endothelial growth factor (VEGF) inhibitors are the most promising anti‐angiogenic agents used increasingly in the clinic. However, to be efficient, anti‐VEGF agents need to be associated with classic chemotherapy. Exploring gene regulation in tumor cells during anti‐angiogenesis might help to comprehend the molecular basis of response to treatment. To generate a defined anti‐angiogenic condition in vivo, we transfected human glioma cells with short‐interfering RNAs against VEGF‐A and implanted them on the chick chorio‐allantoic membrane. Gene regulation in avascular tumors was studied using human Affymetrix™ GeneChips. Potentially important genes were further studied in glioma patients. Despite strong VEGF inhibition, we observed recurrent formation of small, avascular tumors. CHI3L2, IL1B, PI3/elafin and CHI3L1, which encodes for YKL‐40, a putative prognosticator for various diseases, including cancer, were strongly up‐regulated in avascular glioma. In glioblastoma patients, these genes showed coregulation and their expression differed significantly from low‐grade glioma. Importantly, high levels of CHI3L1 (p = 0.036) and PI3/elafin mRNA (p = 0.0004) were significantly correlated with poor survival. Cox regression analysis further confirmed that PI3 and CHI3L1 levels are survival markers independent from patient age and sex. Elafin‐positive tumor cells were only found in glioblastoma, where they were clustered around necrotic areas. PI3/elafin is strongly induced by serum deprivation and hypoxia in U87 glioma cells in vitro. Our results indicate that anti‐angiogenesis in experimental glioma drives expression of critical genes which relate to disease aggressiveness in glioblastoma patients. In particular, CHI3L1 and PI3/elafin may be useful as new prognostic markers and new therapeutic targets. © 2007 Wiley‐Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Saidi

Javerzat

Bellahcène

et al. 2007

Intl Journal of Cancer

101

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“…In einigen höhergradigen Chondro sarkomen lassen sich fokal zusätzlich in trakartilaginäre Blutgefäße nachweisen [1,10] . 3 a-f) mit hohem MPI in Enchondromen und konventionellen Chondrosarkomen (>70%), in dediffe renzierten Chondrosarkomen überra schenderweise sogar mit einem signifi kant noch höheren MPI (>90%) als Aus druck der unterschiedlichen Natur dieser Entitäten [12].…”

Section: Grundlagen Der Angiogeneseunclassified

“…B. Mammakarzi nomen [17], in Chondrosarkomen nicht herunterreguliert, und es besteht kei ne Korrelation mit der Expression von VEGFA [10]. Anders als bei der Expres sion von VEGFA lassen sich auch kei ne Unterschiede in der ADAMTS1Ex pression in konventionellen und dediffe renzierten Chondrosarkomen nachwei sen. Auch wenn die ADAMTS1Expres sion in Enchondromen niedriger ist als in Chondrosarkomen [10], ist auch hier mit eine sichere differenzialdiagnostische Abgrenzung gegenüber Chondrosarko men Grad I nicht möglich.…”

Section: Expression Von Angiogenesefaktoren In Kartilaginären Tumorenunclassified

“…Obwohl Knorpelgewebe und Knorpeltumoren wegen des Sauer stoffdiffusionslimits in der Knorpelmatrix als hypoxisch gelten kann, sind Knorpel zellen offenbar dennoch Hypoxiesen sibel und reagieren auf Hypoxie mit der Regulation von HIF1 und VEGFA [15,19]. In Chondrosarkomzellen [9] konn ten wir unter zunehmender Hypoxie ei ne Hochregulation der Expression von VEGFA bei gleichbleibender Expression von ADAMTS1 nachweisen, was auf ei ne VEGFAunabhängige Regulation von ADAMTS1 hinweist [10].…”

Section: Regulation Angiogener Faktoren Im Zellkulturmodellunclassified

“…In Chondrosarkomzellen konnten wir bei Stimulation mit IL1β eine Hochregu lation von VEGFA bei gleichzeitiger Her unterregulation von ADAMTS1 nachwei sen [10] …”

Section: Regulation Angiogener Faktoren Im Zellkulturmodellunclassified

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Angiogenese in Knorpeltumoren

Kalinski

Roessner

2010

Pathologe

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Expression of ADAMTS1 in endothelial cells is induced by shear stress and suppressed in sprouting capillaries

Hohberg

Knöchel

Hoffmann

et al. 2010

Journal Cellular Physiology

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ADAMTS1 inhibits capillary sprouting, and since capillary sprouts do not experience the shear stress caused by blood flow, this study undertook to clarify the relationship between shear stress and ADAMTS1. It was found that endothelial cells exposed to shear stress displayed a strong upregulation of ADAMTS1, dependent upon both the magnitude and duration of their exposure. Investigation of the underlying pathways demonstrated involvement of phospholipase C, phosphoinositide 3-kinase, and nitric oxide. Forkhead box protein O1 was identified as a likely inhibitor of the system, as its knockdown was followed by a slight increase in ADAMTS1 expression. In silico prediction displayed a transcriptional binding site for Forkhead box protein O1 in the promotor region of the ADAMTS1 gene, as well as sites for nuclear factor 1, SP1, and AP-1. The anti-angiogenic effects of ADAMTS1 were attributed to its cleavage of thrombospondin 1 into a 70-kDa fragment, and a significant enhancement of this fragment was indeed demonstrated by immunoblotting shear stress-treated cells. Accordingly, scratch wound closure displayed a slowdown in conditioned medium from shear stress-treated endothelial cells, an effect that could be completely blocked by a knockdown of thrombospondin 1 and partially blocked by a knockdown of ADAMTS1. Non-perfused capillary sprouts in rat mesenteries stained negative for ADAMTS1, while vessels in the microcirculation that had already experienced blood flow yielded the opposite results. The shear stress-dependent expression of ADAMTS1 in vitro was therefore also demonstrated in vivo and thereby confirmed as a mechanism connecting blood flow with the regulation of angiogenesis.

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ADAMTS1 is regulated by interleukin-1β, not by hypoxia, in chondrosarcoma

Cited by 24 publications

References 23 publications

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Experimental anti‐angiogenesis causes upregulation of genes associated with poor survival in glioblastoma

Angiogenese in Knorpeltumoren

Expression of ADAMTS1 in endothelial cells is induced by shear stress and suppressed in sprouting capillaries

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