2012
DOI: 10.1158/0008-5472.can-12-1229
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Lymphatic Reprogramming by Kaposi Sarcoma Herpes Virus Promotes the Oncogenic Activity of the Virus-Encoded G-protein–Coupled Receptor

Abstract: Kaposi sarcoma (KS), the most common cancer in HIV-positive individuals, is caused by endothelial transformation mediated by the KS herpes virus (KSHV)-encoded G-protein coupled receptor (vGPCR). Infection of blood vascular endothelial cells (BECs) by KSHV reactivates an otherwise silenced embryonic program of lymphatic differentiation. Thus, KS tumors express numerous lymphatic endothelial cell (LEC)-signature genes. A key unanswered question is how lymphatic reprogramming by the virus promotes tumorigenesis … Show more

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Cited by 24 publications
(23 citation statements)
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“…Figure 6C shows a succinct list of the most regulated genes in LEC-219s identified by our RNA-seq approach. The host genes previously reported to be modulated in KSHV-infected endothelial cells are depicted in bold (72,(75)(76)(77)(78)(79). The full list of KSHV-regulated genes is available in Data Set S3 in the supplemental material.…”
Section: Resultsmentioning
confidence: 99%
“…Figure 6C shows a succinct list of the most regulated genes in LEC-219s identified by our RNA-seq approach. The host genes previously reported to be modulated in KSHV-infected endothelial cells are depicted in bold (72,(75)(76)(77)(78)(79). The full list of KSHV-regulated genes is available in Data Set S3 in the supplemental material.…”
Section: Resultsmentioning
confidence: 99%
“…Tumor growth studies were performed as described previously (10). Briefly, three million BCPAP-Ctr and BAPAP-Prx cells were subcutaneously injected into the left and right back skin area of NOD-SCID IL2Rγnull mice (the Jackson Laboratory).…”
Section: Methodsmentioning
confidence: 99%
“…Considering the major role of inflammatory chemokines in KS pathogenesis and that LECs express the atypical chemokine receptor D6 (14), analysis of its expression was performed on biopsies of KS lesions. D6 was found expressed by HHV8-infected spindle-shaped KS cells, and its expression was inversely correlated with tumor aggressiveness, both when comparing maculonodular KS lesions retrospectively classified according to their progression rate (group A vs. group B stage I lesions) and when comparing maculonodular lesions of HIV-seronegative and HIV-seropositive patients, who typically show a slow and rapid progression rate, respectively.…”
Section: Discussionmentioning
confidence: 99%
“…KS tumor cells, also referred to as spindle cells for their shape, are considered to be derived from the LEC lineage and express several LEC markers, including VEGFR3, LYVE-1, and PROX1 (13). It has been shown that KS can also derive from HHV8-infected blood vascular cells that undergo a lymphatic reprogramming to create a more favorable microenvironment for tumor growth (14). Even though HHV8 infection is widespread, KS occurs only sporadically in immunocompetent individuals as classical KS, which is usually characterized by slow-progressing skin lesions with limited dissemination ability.…”
Section: Introductionmentioning
confidence: 99%