Angiogenesis and development of adipose tissue

Christiaens, Valerie; Lijnen, H.R.

doi:10.1016/j.mce.2009.08.006

Cited by 192 publications

(171 citation statements)

References 98 publications

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“…The expression of many angiogenesis regulatory factors changes during adipogenesis. 32 TSP-1 is consistently found in the adipose tissue secretome. [33][34][35] TSP-1 levels are modulated during the differentiation of preadipocyte into adipocytes.…”

Section: Discussionmentioning

confidence: 93%

Antiangiogenic activity of trabectedin in myxoid liposarcoma: Involvement of host TIMP‐1 and TIMP‐2 and tumor thrombospondin‐1

Dossi

Frapolli

Giandomenico

et al. 2014

Intl Journal of Cancer

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Trabectedin is a marine natural product, approved in Europe for the treatment of soft tissue sarcoma and relapsed ovarian cancer. Clinical and experimental evidence indicates that trabectedin is particularly effective against myxoid liposarcomas where response is associated to regression of capillary networks. Here, we investigated the mechanism of the antiangiogenic activity of trabectedin in myxoid liposarcomas. Trabectedin directly targeted endothelial cells, impairing functions relying on extracellular matrix remodeling (invasion and branching morphogenesis) through the upregulation of the inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2. Increased TIMPs synthesis by the tumor microenvironment following trabectedin treatment was confirmed in xenograft models of myxoid liposarcoma. In addition, trabectedin upregulated tumor cell expression of the endogenous inhibitor thrombospondin-1 (TSP-1, a key regulator of angiogenesis-dependent dormancy in sarcoma), in in vivo models of myxoid liposarcomas, in vitro cell lines and primary cell cultures from patients' myxoid liposarcomas. Chromatin Immunoprecipitation analysis showed that trabectedin displaced the master regulator of adipogenesis C/EBPb from the TSP-1 promoter, indicating an association between the upregulation of TSP-1 and induction of adipocytic differentiation program by trabectedin. We conclude that trabectedin inhibits angiogenesis through multiple mechanisms, including directly affecting endothelial cells in the tumor microenvironment-with a potentially widespread activity-and targeting tumor cells' angiogenic activity, linked to a tumor-specific molecular alteration.Trabectedin (Yondelis; ET-743) is a tetrahydroisoquinoline alkaloid isolated from the marine tunicate Ecteinascidia turbinate and now obtained by chemical synthesis.1 It has been approved in Europe for the treatment of advanced or metastatic soft tissue sarcoma and relapsed ovarian cancer, and is currently undergoing phase II trials for several other tumors.Although not yet fully elucidated, its mechanism of action appears different from other antitumor DNA-damaging agents. It binds to N2 of guanine in the minor groove of DNA and interacts with DNA-binding proteins such as DNA repair proteins and transcription factors.1 It affects transcription regulation in a gene-and promoter-dependent fashion in both cancer and normal cells (i.e., macrophages).1-4 As a result trabectedin has a dual antineoplastic effect. It directly targets tumor cells and impairs the recruitment, viability and activity of stroma cells, particularly monocytes/macrophages, 4,5 profoundly affecting the tumor microenvironment, and depriving the tumor of the inflammatory-mediated support.Although trabectedin has shown activity against several types of soft tissue sarcomas, myxoid liposarcomas are the most sensitive to the drug. 6 Myxoid liposarcomas are characterized by chromosomal translocations, most frequently the translocation t(12;16)(q13;p11) leading to the formation of a fusion oncoprotein between FUS (fu...

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Section: Discussionmentioning

confidence: 93%

Antiangiogenic activity of trabectedin in myxoid liposarcoma: Involvement of host TIMP‐1 and TIMP‐2 and tumor thrombospondin‐1

Dossi

Frapolli

Giandomenico

et al. 2014

Intl Journal of Cancer

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“…port the enlarged and expanded adipocyte pool, an appropriate stromovascular network must form in parallel (3)(4)(5). It is possible that expansion of the vascular network may actually precede adipocyte growth, as is known to occur during embryonic development, when the formation of the adipose tissue vascular network precedes the emergence of adipocytes (6).…”

mentioning

confidence: 99%

Control of Adipose Tissue Expandability in Response to High Fat Diet by the Insulin-like Growth Factor-binding Protein-4

Gealekman

Gurav

Chouinard

et al. 2014

Journal of Biological Chemistry

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“…Hypoxia has recently been proposed as a possible initiator instigating macrophage infiltration and inflammation in obese WAT (5)(6)(7). The expansion of WAT is critically dependent on the microvasculature and angiogenesis in this tissue (8,9). It has been suggested that the enlargement of adipocyte size in obesity exceeds the normal oxygen diffusion distance and compromises the effective oxygen supply from the vasculature, leading to localized hypoxia (10).…”

mentioning

confidence: 99%

Adipose Tissue-specific Inhibition of Hypoxia-inducible Factor 1α Induces Obesity and Glucose Intolerance by Impeding Energy Expenditure in Mice*

Zhang¹,

Lam²,

et al. 2010

Journal of Biological Chemistry

100

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Hypoxia in adipose tissue has been postulated as a possible contributor to obesity-related chronic inflammation, insulin resistance, and metabolic dysfunction. HIF1␣ (hypoxia-inducible factor 1␣), a master signal mediator of hypoxia response, is elevated in obese adipose tissue. However, the role of HIF1␣ in obesity-related pathologies remains to be determined. Here we show that transgenic mice with adipose tissue-selective expression of a dominant negative version of HIF1␣ developed more severe obesity and were more susceptible to high fat diet-induced glucose intolerance and insulin resistance compared with their wild type littermates. Obesity in the transgenic mice was attributed to impaired energy expenditure and reduced thermogenesis. Histological examination of interscapular brown adipose tissue (BAT) in the transgenic mice demonstrated a markedly increased size of lipid droplets and decreased mitochondrial density in adipocytes, a phenotype similar to that in white adipose tissue. These changes in BAT of the transgenic mice were accompanied by decreased mitochondrial biogenesis and reduced expression of key thermogenic genes. In the transgenic mice, angiogenesis in BAT was decreased but was little affected in white adipose tissue. These findings support an indispensable role of HIF1␣ in maintaining the thermogenic functions of BAT, possibly through promoting angiogenesis and mitochondrial biogenesis in this tissue.

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Angiogenesis and development of adipose tissue

Cited by 192 publications

References 98 publications

Antiangiogenic activity of trabectedin in myxoid liposarcoma: Involvement of host TIMP‐1 and TIMP‐2 and tumor thrombospondin‐1

Antiangiogenic activity of trabectedin in myxoid liposarcoma: Involvement of host TIMP‐1 and TIMP‐2 and tumor thrombospondin‐1

Control of Adipose Tissue Expandability in Response to High Fat Diet by the Insulin-like Growth Factor-binding Protein-4

Adipose Tissue-specific Inhibition of Hypoxia-inducible Factor 1α Induces Obesity and Glucose Intolerance by Impeding Energy Expenditure in Mice*

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