Kaposi's sarcoma-associated herpesvirus-positive primary effusion lymphoma tumor formation in NOD/SCID mice is inhibited by neomycin and neamine blocking angiogenin's nuclear translocation.

[primary effusion lymphoma]

Angiogenin (ANG ) is a 14 -kDa multifunctional proangiogenic secreted protein whose expression level correlates with the aggressiveness of several tumors . We observed increased ANG expression and secretion in endothelial cells during de novo infection with Kaposi 's sarcoma -associated herpesvirus (KSHV ), in cells expressing only latency-associated nuclear antigen 1 (LANA -1 ) protein , and in KSHV latently infected primary effusion lymphoma (PEL ) BCBL-1 and BC -3 cells . Inhibition of phospholipase C Î³ (PLCÎ³ ) mediated ANG 's nuclear translocation by neomycin , an aminoglycoside antibiotic (not G 418 -neomicin ), resulted in reduced KSHV latent gene expression , increased lytic gene expression , and increased cell death of KSHV (+) PEL and endothelial cells . ANG detection in significant levels in KS and PEL lesions highlights its importance in KSHV pathogenesis . To assess the in vivo antitumor activity of neomycin and neamine (a nontoxic derivative of neomycin ), BCBL-1 cells were injected intraperitoneally into NOD /SCID mice . We observed significant extended survival of mice treated with neomycin or neamine . Markers of lymphoma establishment , such as increases in animal body weight , spleen size , tumor cell spleen infiltration , and ascites volume , were observed in nontreated animals and were significantly diminished by neomycin or neamine treatments . A significant decrease in LANA -1 expression , an increase in lytic gene expression , and an increase in cleaved caspase-3 were also observed in neomycin- or neamine-treated animal ascitic cells . These studies demonstrated that ANG played an essential role in KSHV latency maintenance and BCBL-1 cell survival in vivo , and targeting ANG function by neomycin /neamine to induce the apoptosis of cells latently infected with KSHV is an attractive therapeutic strategy against KSHV-associated malignancies .

Diseases
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Diseases presenting "only latency-associated nuclear antigen" symptom

primary effusion lymphoma

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