Weibel-Palade bodies in Kaposi's sarcoma cells.

Marquart, Karl-Horst

doi:10.1136/jcp.40.8.933-a

Cited by 5 publications

(4 citation statements)

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“…Taken together, our findings indicate that KSHV infection can reprogram MSCs to acquire endothelial markers and functions through MEndT. However, KSHV-induced endothelial lineage differentiation is incomplete as cells retain specific mesenchymal markers and lack endothelial cell specialized organelles Weibel–Palade bodies (WPBs), exhibiting striking resemblance to KS spindle cells [8].…”

Section: Resultsmentioning

confidence: 98%

“…However, KS spindle cells also express other markers including smooth muscle cell (αSAM), macrophage (CD68), dendritic cell (Factor XIII) and mesenchymal stem cell (Nestin and CD29) markers, suggesting that KS cells do not faithfully represent an endothelial cell lineage [6]. Besides, KS spindle cells display intriguing characteristics of progenitor or immature endothelial cells – the expression of endothelial progenitor cell markers and lack of Weibel-Palade bodies (WPB) regarded as a marker for mature vascular endothelium [7, 8]. The remarkable heterogeneity of KS raised a hypothesis that KS spindle cells may originate from mesenchymal stem cells (MSCs) or precursors of vascular cells [9, 10].…”

Section: Introductionmentioning

confidence: 99%

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Kaposi’s Sarcoma-associated Herpesvirus vFLIP Promotes MEndT to Generate Hybrid M/E State for Tumorigenesis

Chen

Ding

et al. 2021

Preprint

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Kaposi’s sarcoma (KS) is an angioproliferative and invasive tumor caused by Kaposi’s sarcoma-associated herpesvirus (KSHV). The cellular origin of KS tumor cells remains contentious. Recently, evidence has accrued indicating that KS may arise from KSHV-infected mesenchymal stem cells (MSCs) through mesenchymal-to-endothelial transition (MEndT), but the transformation process has been largely unknown. In this study, we investigated the KSHV-mediated MEndT process and found that KSHV infection rendered MSCs incomplete endothelial lineage differentiation and formed hybrid mesenchymal/endothelial (M/E) state cells characterized by simultaneous expression of mesenchymal markers PDGFRA/Nestin and endothelial markers PDPN/CD31. The hybrid M/E cells have acquired high tumorigenic properties in vitro and the potential to form KS-like tumors after transplanted in mice under renal capsules. These results faithfully recapitulate Kaposi’s sarcoma where proliferating KS spindle-shaped cells and the cells that line KS-specific aberrant vessels were also found to exhibit a hybrid M/E state. Furthermore, the genetic analysis identified KSHV-encoded FLICE inhibitory protein (vFLIP) as a crucial regulator controlling KSHV-induced MEndT and generating hybrid M/E state cells for tumorigenesis. Overall, KSHV-mediated MEndT that transforms MSCs to tumorigenic hybrid M/E state cells driven by vFLIP is an essential event in Kaposi’s sarcomagenesis.Author SummaryKaposi’s sarcoma manifests as multifocal lesions with spindle cell proliferation, intense angiogenesis, and erythrocyte extravasation. Although the origin and true malignant nature of KS remains contentious, it is established that KSHV infection with concomitant viral oncogene expression in normal cell progenitors causes KS. The mechanism of KSHV oncogenesis could be revealed through reproduction of KS by infection of normal cells. This study reports that the KSHV infection of mesenchymal stem cells initiates mesenchymal-to-endothelial transition (MEndT) that generates mesenchymal/endothelial (M/E) hybrid state cells. The hybrid M/E cells acquired high tumorigenic properties, including tumor initiation, angiogenesis, migration, and the potential to form KS-like tumors after transplanted in mice. This finding faithfully recapitulates Kaposi’s sarcoma where proliferating KS spindle cells and the cells that line KS-specific aberrant vessels are also found to exhibit the hybrid M/E state. We also found that KSHV-encoded viral FLICE inhibitory protein (vFLIP) plays a crucial role in promoting MEndT and the generation of M/E state cells. These results provide a new layer of evidence for MSCs being the cell source of KS spindle cells and reveal novel insight into KS pathogenesis and viral tumorigenesis.

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Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Kaposi’s Sarcoma-associated Herpesvirus vFLIP Promotes MEndT to Generate Hybrid M/E State for Tumorigenesis

Chen

Ding

et al. 2021

Preprint

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“…MSCs to acquire endothelial markers and functions through MEndT. However, KSHVinduced endothelial lineage differentiation is incomplete as cells retain specific mesenchymal markers and lack endothelial cell specialized organelles Weibel-Palade bodies (WPBs), exhibiting a striking resemblance to KS spindle cells [8].…”

Section: Pdlscs (Fig 4f) Taken Together Our Findings Indicate That Kshv Infection Can Reprogrammentioning

confidence: 99%

“…However, KS spindle cells also express other markers including smooth muscle cell (α-SAM), macrophage (CD68), dendritic cell (Factor XIII) and mesenchymal stem cell (Nestin and CD29) markers, suggesting that KS cells do not faithfully represent an endothelial cell lineage [ 6 ]. Besides, KS spindle cells display intriguing characteristics of progenitor or immature endothelial cells—the expression of endothelial progenitor cell markers and lack of Weibel-Palade bodies (WPB) regarded as a marker for mature vascular endothelium [ 7 , 8 ]. The remarkable heterogeneity of KS raised a hypothesis that KS spindle cells may originate from mesenchymal stem cells (MSCs) or precursors of vascular cells [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Kaposi’s sarcoma-associated herpesvirus vFLIP promotes MEndT to generate hybrid M/E state for tumorigenesis

et al. 2021

View full text Add to dashboard Cite

Kaposi sarcoma (KS) is an angioproliferative and invasive tumor caused by Kaposi sarcoma-associated herpesvirus (KSHV). The cellular origin of KS tumor cells remains contentious. Recently, evidence has accrued indicating that KS may arise from KSHV-infected mesenchymal stem cells (MSCs) through mesenchymal-to-endothelial transition (MEndT), but the transformation process has been largely unknown. In this study, we investigated the KSHV-mediated MEndT process and found that KSHV infection rendered MSCs incomplete endothelial lineage differentiation and formed hybrid mesenchymal/endothelial (M/E) state cells characterized by simultaneous expression of mesenchymal markers Nestin/PDGFRA/α-SAM and endothelial markers CD31/PDPN/VEGFR2. The hybrid M/E cells have acquired tumorigenic phenotypes in vitro and the potential to form KS-like lesions after being transplanted in mice under renal capsules. These results suggest a homology of KSHV-infected MSCs with Kaposi sarcoma where proliferating KS spindle-shaped cells and the cells that line KS-specific aberrant vessels were also found to exhibit the hybrid M/E state. Furthermore, the genetic analysis identified KSHV-encoded FLICE inhibitory protein (vFLIP) as a crucial regulator controlling KSHV-induced MEndT and generating hybrid M/E state cells for tumorigenesis. Overall, KSHV-mediated MEndT that transforms MSCs to tumorigenic hybrid M/E state cells driven by vFLIP is an essential event in Kaposi sarcomagenesis.

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Tumours

Corrin

Nicholson

2011

Pathology of the Lungs

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Weibel-Palade bodies in Kaposi's sarcoma cells.

Abstract: Weibel-Palade bodies in Kaposi's sarcoma cells Russell Jones et al recently reported immunohistochemical findings which favour the hypothesis that Kaposi's sarcoma cells are derived from lymphatic endothelium.'

Cited by 5 publications

References 2 publications

Kaposi’s Sarcoma-associated Herpesvirus vFLIP Promotes MEndT to Generate Hybrid M/E State for Tumorigenesis

Kaposi’s Sarcoma-associated Herpesvirus vFLIP Promotes MEndT to Generate Hybrid M/E State for Tumorigenesis

Kaposi’s sarcoma-associated herpesvirus vFLIP promotes MEndT to generate hybrid M/E state for tumorigenesis

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