Inhibition of tumor cell surface ATP synthesis by pigment epithelium-derived factor: implications for antitumor activity.
Inhibition of tumor cell surface ATP synthesis by pigment epithelium-derived factor: implications for antitumor activity.
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色素上皮衍生因子抑制肿瘤细胞表面 ATP 合成：抗肿瘤活性的影响。
DOI：
10.3892/ijo.2012.1431
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发表时间：
2012-07
影响因子：
5.2
通讯作者：
Becerra SP
中科院分区：
文献类型：
--
作者：
Deshpande M;Notari L;Subramanian P;Notario V;Becerra SP
最近，我们发现抗血管生成色素上皮源性因子可以结合催化的F1-β合酶亚基，并抑制内皮细胞表面的ATP合酶活性。该因子还可以限制肿瘤的生长、侵袭和转移，并可直接诱导多种类型的肿瘤细胞死亡。活跃的细胞表面ATP合成酶也存在于某些肿瘤细胞中，其ATP产物被认为是肿瘤生长的刺激因素。本研究旨在阐明细胞外PEDF与肿瘤细胞表面ATP合成酶相互作用的生物学意义。T24人膀胱癌细胞在含有人重组PEDF蛋白的培养液中孵育48-96h后，细胞活力显著降低，并呈浓度依赖关系，通过微电子系统实时细胞阻抗、显微成像和活细胞生物标志物监测。完整的肿瘤细胞表现出细胞表面的ATP合成活性，这种活性被F1/F0-ATP合成酶的特异性抑制剂Piceatanyl抑制。免疫印迹显示，F1-β合酶的亚基存在于这些细胞的质膜部分。有趣的是，预先用PEDF孵育肿瘤细胞以浓度依赖的方式抑制细胞表面ATP合成酶的活性。PEDF衍生的肽34-mer降低了肿瘤细胞的活力，并抑制了细胞外ATP的合成，其程度与全长PEDF相同。此外，三磷酸腺苷的加入减轻了PEDF介导的肿瘤细胞活力的下降和内皮细胞管形成的抑制。这些结果表明，PEDF是一种新型的肿瘤细胞表面ATP合成酶活性的抑制剂，对肿瘤细胞具有细胞毒作用，这些性质的结构决定因素位于PEDF多肽的34-聚体内。这些数据有力地表明，PEDF的34聚体区域与肿瘤细胞表面ATP合成酶之间的相互作用在促进肿瘤细胞死亡方面发挥了作用。
Recently, we have shown that the antiangiogenic pigment epithelium-derived factor (PEDF) can bind the catalytic β-subunit of F1-ATP synthase and inhibit endothelial cell surface ATP synthase activity. This factor can additionally restrict tumor growth, invasion and metastasis, and can directly induce death on several tumor cell types. Active cell surface ATP synthase is also present in certain tumor cells and its ATP product is considered a stimulus for tumor growth. The present study aimed to elucidate the biological implications of the interactions between the extracellular PEDF and tumor cell surface ATP synthase. Incubation of T24 human urinary bladder carcinoma cells in media containing human recombinant PEDF protein for 48–96 h dramatically decreased cell viability in a concentration-dependent fashion as monitored by real-time cell impedance with a microelectronic system, microscopic imaging and biomarkers of live cells. Intact tumor cells exhibited cell surface ATP synthesis activity, which was inhibited by piceatannol, a specific inhibitor of F1/F0-ATP synthase. Immunoblotting revealed that the β subunit of F1-ATP synthase was present in plasma membrane fractions of these cells. Interestingly, pre-incubation of tumor cells with PEDF inhibited the activity of cell surface ATP synthase in a concentration-dependent fashion. The PEDF-derived peptide 34-mer decreased tumor cell viability and inhibited extracellular ATP synthesis to the same extent as full-length PEDF. Moreover, ATP additions attenuated both the PEDF-mediated decrease in tumor cell viability and the inhibition of endothelial cell tube formation. The results lead to conclude that PEDF is a novel inhibitor of tumor cell surface ATP synthase activity that exhibits a cytotoxic effect on tumor cells, and that the structural determinants for these properties are within the peptide region 34-mer of the PEDF polypeptide. The data strongly suggest a role for the interaction between the 34-mer region of PEDF and tumor cell-surface ATP synthase in promoting tumor cell death.
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影响因子：
4.4
作者：
Amaral J;Becerra SP
通讯作者：
Becerra SP
影响因子：
4.8
作者：
Bernard, Adrien;Gao-Li, Jacqueline;Li, Zhenlin
通讯作者：
Li, Zhenlin
影响因子：
12.8
作者：
Kim, BW;Choo, HJ;Ko, YG
通讯作者：
Ko, YG
DOI：
10.1073/pnas.131067798
发表时间：
2001-06-05
影响因子：
11.1
作者：
Moser, TL;Kenan, DJ;Pizzo, SV
通讯作者：
Pizzo, SV
影响因子：
4.8
作者：
Alberdi, E;Aymerich, MS;Becerra, SP
通讯作者：
Becerra, SP