Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration.
Burkitt lymphoma expresses oncofetal chondroitin sulfate without being a reservoir for placental malaria sequestration.
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DOI：
10.1002/ijc.30575
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发表时间：
2017-04-01
影响因子：
6.4
通讯作者：
Salanti A
中科院分区：
文献类型：
--
作者：
Agerbaek MØ;Pereira MA;Clausen TM;Pehrson C;Oo HZ;Spliid C;Rich JR;Fung V;Nkrumah F;Neequaye J;Biggar RJ;Reynolds SJ;Tosato G;Pullarkat ST;Ayers LW;Theander TG;Daugaard M;Bhatia K;Nielsen MA;Mbulaiteye SM;Salanti A
伯基特淋巴瘤（BL）是恶性疟流行区常见的恶性肿瘤。我们先前已经发现VAR2CSA蛋白存在于疟疾感染的红细胞上，并促进与胎盘的高度特异性结合。OfCS不存在于其他非恶性组织中，因此VAR2CSA通常促进孕妇中的寄生虫隔离和积累。在这项研究中，我们表明，VAR2CSA的特异性受体，癌胚硫酸软骨素（ofCS），同样存在于BL组织和细胞系。因此，我们探讨了BL中的ofCS是否可以作为表达VAR2CSA的感染红细胞的锚定位点。与胎盘相反，我们没有发现BL组织中受感染红细胞体内隔离的证据。此外，我们发现，VAR2CSA特异性抗体滴度在儿童与地方性BL要低于对照组儿童从同一疟疾流行区。BL组织中ofCS的丰富存在和非恶性组织中ofCS的缺乏促使我们检查重组VAR2CSA是否可用于靶向BL。我们证实了VAR2CSA与BL衍生的细胞的结合，并显示VAR2CSA药物缀合物在体外有效地杀死BL衍生的细胞系。这些结果确定ofCS作为一种新的治疗BL目标，并强调如何VAR2CSA可以用作一种工具，用于发现新的方法，指导BL治疗。
Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria-infected erythrocytes and facilitates a highly specific binding to the placenta. OfCS is absent from other non-malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines. We therefore explored whether ofCS in BL could act as anchor-site for VAR2CSA-expressing infected erythrocytes. In contrast to the placenta, we found no evidence of in vivo sequestering of infected erythrocytes in the BL tissue. Furthermore, we found VAR2CSA specific antibody titers in children with endemic BL to be lower than in control children from the same malaria endemic region. The abundant presence of ofCS in BL tissue and the absence of ofCS in non-malignant tissue, encouraged us to examine whether recombinant VAR2CSA could be used to target BL. We confirmed the binding of VAR2CSA to BL-derived cells and showed that a VAR2CSA drug conjugate efficiently killed the BL-derived cell lines in vitro. These results identify ofCS as a novel therapeutic BL target and highlight how VAR2CSA could be used as a tool for the discovery of novel approaches for directing BL therapy.