Kaposi's Sarcoma-Like Tumors in a Human Herpesvirus 8 ORF74 Transgenic Mouse

Guo, Hong; Sadowska, Mariola; Reid, William; Tschachler, Erwin; Hayward, Gary S.; Reitz, Marvin S.

doi:10.1128/jvi.77.4.2631-2639.2003

Cited by 137 publications

(124 citation statements)

References 45 publications

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“…In addition, the genome encodes a seven-transmembrane-spanning G protein-coupled receptor (GPCR) with extensive sequence similarity to cellular chemokine receptors [108]. When expressed in NIH 3T3 fibroblasts, this gene increases their ability to grow in soft agar and to induce tumor formation in nude mice [109]. GPCR increases secretion of vascular endothelial growth factor and activation of the ERK1/2 (p44/42) mitogen-activated protein kinase signaling pathway [110].…”

Section: Pathobiologymentioning

confidence: 99%

“…Endothelial cells that express this gene become immortalized with constitutive activation of the VEGF-receptor 2 (KDR) [111]. In addition, this gene can cause KS-like lesions in nude mice [109], and over-expression within hematopoietic cells results in angioproliferative lesions, resembling those found in KS [112]. These are yet more examples of viral factors with the potential of altering cellular phenotype in the absence of viral replication.…”

Section: Pathobiologymentioning

confidence: 99%

See 1 more Smart Citation

Pathology of Pulmonary Hypertension

Tuder

Marecki

Richter

et al. 2013

Clinics in Chest Medicine

220

107

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Section: Pathobiologymentioning

confidence: 99%

Section: Pathobiologymentioning

confidence: 99%

Pathology of Pulmonary Hypertension

Tuder

Marecki

Richter

et al. 2013

Clinics in Chest Medicine

220

107

View full text Add to dashboard Cite

“…This receptor is constitutively signal-coupled, but its signal-coupling can be further augmented when bound to ELR+ chemokine ligands, CXCL8 or CXCL1 (39)(40)(41). The relevance of this receptor to pathogenesis of Kaposi's sarcoma was established using transgenic mice expressing KSHV-GPCR, which spontaneously develop angioproliferative KS-like lesions (42,43). In further support of this contention is the finding that a point mutation of CXCR2, but not CXCR1, results in constitutive signalling of the receptor and cellular transformation of transfected cells in a similar manner as KSHV-GPCR (37).…”

Section: Virally Encoded Chemokine Receptorsmentioning

confidence: 99%

Chemokines as mediators of angiogenesis

Mehrad¹,

Keane²,

Strieter³

2007

Thromb Haemost

180

145

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SummaryChemokines were originally described as cytokines that mediate leukocyte recruitment to sites of inflammation. Members of a subgroup of chemokines, the CXC family, also play a critical role in both physiologic and pathologic angiogenesis, including in the context of chronic inflammation, fibrosis, and malignancy. A unique feature of this family of cytokines is that, on the basis of their structure and receptor binding, individual ligands display either angiogenic or angiostatic biological activity in the regulation of angiogenesis. In this review, we summarize the key literature in this growing field.

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“…Expression of KSHV-GPCR stimulates proliferation in rat fibroblasts (Arvanitakis et al, 1997) and causes transformation in NIH 3T3 cells and tumors, when transfected cells are injected into nude mice (Bais et al, 1998). Furthermore, transgenic mice expressing KSHV-GPCR within hematopoetic cells or endothelial cells develop angioproliferative lesions in multiple organs resembling the Kaposi's sarcoma (Yang et al, 2000;Guo et al, 2003;Montaner et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

KSHV-GPCR and CXCR2 transforming capacity and angiogenic responses are mediated through a JAK2-STAT3-dependent pathway

et al. 2005

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The Kaposi's sarcoma herpesvirus encodes a G-proteincoupled chemokine receptor termed KSHV-GPCR. Expression of this constitutively active GPCR leads to cell transformation and vascular overgrowth characteristic of Kaposi's sarcoma. Previously, we have shown that CXCR2, the closest human homolog, is similarly able to transform cells if continuously stimulated or constitutively activated by amino-acid exchange D138V of the DRY sequence. Here, we demonstrate that STAT3 activation is a prerequisite for transformation in KSHV-GPCR and CXCR2 transfected NIH 3T3 cells. In KSHV-GPCR and D138V transfected cells, STAT-3 is constitutively phosphorylated on Tyr 705 . In CXCR2 transfected NIH 3T3 cells and human microvascular endothelial cells (HMEC), which express the CXCR2 constitutively, STAT3 is phosphorylated upon stimulation with IL-8 (CXCL8). Focus formation in NIH 3T3 cells transfected with the KSHV-GPCR, CXCR2, or the D138V mutant, was blocked by the specific JAK2 inhibitor AG490. Typical functions of the CXCR2 including actin stress fiber formation, haptotaxis, and the angiogenic response in HMEC shown by tube formation in Matrigel were blocked by AG490. These data suggest that the transforming capacity and migratory responses that are involved in tumor development, metastasis, and angiogenesis in KSHV or CXCR2-expressing cells is at least partially mediated through a JAK2-STAT3 dependent pathway.

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Kaposi's Sarcoma-Like Tumors in a Human Herpesvirus 8 ORF74 Transgenic Mouse

Cited by 137 publications

References 45 publications

Pathology of Pulmonary Hypertension

Pathology of Pulmonary Hypertension

Chemokines as mediators of angiogenesis

KSHV-GPCR and CXCR2 transforming capacity and angiogenic responses are mediated through a JAK2-STAT3-dependent pathway

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