Cooperative roles for emmprin and LYVE-1 in the regulation of chemoresistance for primary effusion lymphoma.
Cooperative roles for emmprin and LYVE-1 in the regulation of chemoresistance for primary effusion lymphoma.
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卡波西肉瘤相关疱疹病毒是原发性渗出性淋巴瘤（PEL）的病原体，细胞毒性化疗是治疗的标准。与PEL相关的高死亡率可能部分解释为这些肿瘤对化疗的耐药性。膜结合糖蛋白emmprin（CD 147）通过影响转运蛋白表达、运输和相互作用增强肿瘤的化疗耐药性。细胞表面透明质酸和透明质酸受体之间的相互作用也促进了emmprin介导的化学抗性。是否emmprin或透明质酸受体相互作用调节病毒相关恶性肿瘤的化疗耐药性尚不清楚。使用人PEL肿瘤细胞，我们发现PEL对化疗的敏感性与emmprin、淋巴管内皮透明质酸受体-1（LYVE-1）和称为乳腺癌耐药蛋白/ABCG 2（BCRP）的药物转运蛋白的表达成正比，并且emmprin、LYVE-1和BCRP相互作用并共定位于PEL细胞表面。此外，我们发现细胞外基质金属蛋白酶诱导因子通过上调BCRP表达来诱导BEL细胞的化疗耐药性，而针对细胞外基质金属蛋白酶诱导因子、LYVE-1或BCRP的RNA干扰增强了化疗诱导的BEL细胞凋亡。最后，使用小透明质酸寡糖破坏透明质酸-受体相互作用降低了细胞外基质金属蛋白酶诱导因子和BCRP的表达，同时使PEL细胞对化疗敏感。总的来说，这些数据支持细胞外基质金属蛋白酶诱导因子、LYVE-1和BCRP在PEL化疗耐药性中的相互依赖作用。
The Kaposi’s sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), for which cytotoxic chemotherapy represents the standard of care. The high mortality associated with PEL may be explained in part by resistance of these tumors to chemotherapy. The membrane-bound glycoprotein emmprin (CD147) enhances chemoresistance in tumors through effects on transporter expression, trafficking and interactions. Interactions between hyaluronan and hyaluronan receptors on the cell surface also facilitate emmprin-mediated chemoresistance. Whether emmprin or hyaluronan-receptor interactions regulate chemotherapeutic resistance for virus-associated malignancies is unknown. Using human PEL tumor cells, we found that PEL sensitivity to chemotherapy is directly proportional to expression of emmprin, the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and a drug transporter known as the breast cancer resistance protein/ABCG2 (BCRP), and that emmprin, LYVE-1 and BCRP interact with each other and colocalize on the PEL cell surface. In addition, we found that emmprin induces chemoresistance in PEL cells through upregulation of BCRP expression, and RNA interference targeting of emmprin, LYVE-1 or BCRP enhances PEL cell apoptosis induced by chemotherapy. Finally, disruption of hyaluronan-receptor interactions using small hyaluronan oligosaccharides reduces expression of emmprin and BCRP while sensitizing PEL cells to chemotherapy. Collectively, these data support interdependent roles for emmprin, LYVE-1 and BCRP in chemotherapeutic resistance for PEL.
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DOI：
10.1084/jem.20031467
发表时间：
2004-04-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guasparri I;Keller SA;Cesarman E
通讯作者：
Cesarman E
影响因子：
45.3
作者：
Boulanger, E;Gérard, L;Oksenhendler, E
通讯作者：
Oksenhendler, E
DOI：
10.4049/jimmunol.1001857
发表时间：
2010-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Benjamin JT;Carver BJ;Plosa EJ;Yamamoto Y;Miller JD;Liu JH;van der Meer R;Blackwell TS;Prince LS
通讯作者：
Prince LS
影响因子：
5.4
作者：
An, Feng-Qi;Folarin, Hope Merlene;Renne, Rolf
通讯作者：
Renne, Rolf
影响因子：
5.8
作者：
Chen, Yi-Bin;Rahemtullah, Aliyah;Hochberg, Ephraim
通讯作者：
Hochberg, Ephraim