Chemokine receptor expression in EBV-associated lymphoproliferation in hu/SCID mice: implications for CXCL12/CXCR4 axis in lymphoma generation
Chemokine receptor expression in EBV-associated lymphoproliferation in hu/SCID mice: implications for CXCL12/CXCR4 axis in lymphoma generation
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DOI：
10.1182/blood-2004-03-0799
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发表时间：
2005-02-01
期刊：
影响因子：
20.3
通讯作者：
Amadori, A
中科院分区：
文献类型：
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作者：
Piovan, E;Tosello, V;Amadori, A
将来自EB病毒（EBV）血清阳性供体的外周血单核细胞（PBMC）腹膜内注射到严重联合免疫缺陷（SCID）小鼠中引起淋巴瘤（hu/SCID肿瘤）的机制尚不清楚。本研究探讨了趋化因子受体及其配体是否可能参与该实验模型。发现CXCR 4在hu/SCID肿瘤中高度表达; CXCR 4的表面表达主要限于表达CD 23的肿瘤细胞亚群，而CXCR 4配体CXCL 12主要由表达CD 23的肿瘤亚群表达。在体外抑制这种自分泌/旁分泌CXCL 12/CXCR 4轴显著抑制淋巴瘤增殖和存活。此外，CXCL 12在PBMC转移后早期从小鼠腹膜腔回收的细胞中表达，以及通过EBV转化的B细胞表达，但不通过静息或活化的B淋巴细胞表达;此外，淋巴瘤的发展与腹膜腔中存在的鼠CXCL 12水平的急剧增加相关。最后，在体内拮抗CXCL 12/CXCR 4轴强烈地抵消了淋巴瘤的发展。这些研究表明，CXCL 12的表达可能与EBV感染，并建议CXCR 4/CXCL 12轴可能参与EBV相关的淋巴瘤发生过程中的免疫缺陷的主机。(C)2005年，美国血液学会。
The mechanisms by which intraperitoneal injection of peripheral blood mononuclear cells (PBMCs) from Epstein-Barr virus (EBV)-seropositive donors into severe combined immunodeficient (SCID) mice gives rise to lymphomas (hu/SCID tumors) are far from clear. This study addressed whether chemokine receptors and their ligands could be implicated in this experimental model. CXCR4 was found to be highly expressed in hu/SCID tumors; surface expression of CXCR4 was prevalently limited to a tumor cell subset poorly expressing CD23, whereas the CXCR4 ligand, CXCL12, was predominantly expressed by the tumor subpopulation expressing CD23. In vitro inhibition of this autocrine/paracrine CXCL12/CXCR4 axis significantly inhibited lymphoma proliferation and survival. Furthermore, CXCL12 was expressed in cells recovered from the mouse peritoneal cavity early after PBMC transfer as well as by EBV-transformed B cells but not by resting or activated B lymphocytes; also, lymphoma development was associated with a dramatic increase in the levels of murine CXCL12 present in the peritoneal cavity. Finally, antagonizing the CXCL12/CXCR4 axis in vivo strongly counteracted lymphoma development. These studies demonstrate that CXCL12 expression may be associated with EBV infection and suggest that the CXCR4/CXCL12 axis may participate in the EBW-associated lymphomagenesis process in immunodeficient hosts. (C) 2005 by The American Society of Hematology.