Role of vascular endothelial growth factor/vascular permeability factor in the pathogenesis of Kaposi's sarcoma-associated herpesvirus-infected primary effusion lymphomas
Role of vascular endothelial growth factor/vascular permeability factor in the pathogenesis of Kaposi's sarcoma-associated herpesvirus-infected primary effusion lymphomas
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DOI：
10.1182/blood.v94.12.4247
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发表时间：
1999-12-15
期刊：
影响因子：
20.3
通讯作者：
Tosato, G
中科院分区：
文献类型：
--
作者：
Aoki, Y;Tosato, G
原发性渗出性淋巴瘤（PEL）是与卡波西肉瘤相关疱疹病毒（或人疱疹病毒-8）感染相关的罕见淋巴瘤，表现为体腔中的恶性淋巴瘤性渗出。由于PEL更喜欢液体生长，我们假设血管通透性增加将需要积液的形成。我们发现PEL细胞系BC-1、BCP-1和BCBL-1产生高水平的血管内皮生长因子/血管通透性因子，（VEGF/VPF），来自扩增3种VEGF分泌亚型的PEL细胞系的RNA的逆转录酶-聚合酶链反应分析：VEGF/VPF 121、VEGF/VPF 145和VEGF/VPF 165，两种PEL细胞系表达VEGF/VPF受体Flt-1，但VEGF/VPF不刺激这些细胞的增殖，大多数（13/14）对照SCID/beige小鼠腹腔内接种BCBL-1细胞，随后观察或用对照抗体治疗，发展为人细胞来源的渗出性淋巴瘤，伴明显血性腹水。相反，用中和性抗人VEGF/VPF抗体处理的小鼠中没有（0/9）发展腹水和渗出性淋巴瘤。这些结果表明，VEGF/VPF对小鼠中作为渗出性淋巴瘤的BCBL-1生长是关键的，并表明VEGF/VPF刺激血管通透性可能对PEL的发病机理是关键的，（C）1999，美国血液学学会。
primary effusion lymphomas (PELs), which are rare lymphomas associated with Kaposi's sarcoma-associated herpesvirus (or human herpesvirus-8) infection, present as malignant lymphomatous effusions in body cavities. Because PELs prefer liquid growth, we hypothesized that increased vascular permeability would be required for effusions to form. We found that the PEL cell lines BC-1, BCP-1, and BCBL-1 produce high levels of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF), Reverse transcriptase-polymerase chain reaction analysis of RNA from the PEL cell lines amplified the 3 VEGF-secreted isoforms: VEGF/VPF121, VEGF/VPF145, and VEGF/VPF165, Two of the PEL cell lines expressed the VEGF/VPF receptor Flt-1, but VEGF/VPF did not stimulate proliferation in these cells, Most (13/14) control SCID/beige mice inoculated intraperitoneally with BCBL-1 cells and subsequently observed or treated with control antibodies developed effusion lymphoma of human cell origin with prominent bloody ascites. In contrast, none (0/9) of the mice treated with a neutralizing antihuman VEGF/VPF antibody developed ascites and effusion lymphoma. These results demonstrate that VEGF/VPF is critical to BCBL-1 growth as effusion lymphoma in mice and suggest that VEGF/VPF stimulation of vascular permeability may be critical to the pathogenesis of PELs, (C) 1999 by The American Society of Hematology.