Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer.
Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer.
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瘦素信号传导抑制可在雌激素受体阳性或阴性乳腺癌中产生有效的抗肿瘤活性。
DOI：
10.1186/bcr2321
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发表时间：
2009
影响因子：
7.4
通讯作者：
Penichet, Manuel L.
中科院分区：
文献类型：
--
作者：
Gonzalez, Ruben Rene;Watters, Amber;Xu, Yanbo;Singh, Udai P.;Mann, David R.;Rueda, Bo R.;Penichet, Manuel L.
我们先前已表明，用聚乙二醇化瘦素肽受体拮抗剂2（PEG - LPrA2）治疗可降低同基因小鼠中血管内皮生长因子（VEGF）、血管内皮生长因子受体2型（VEGFR2）的表达以及4T1乳腺癌（BC）的生长。在本研究中，使用PEG - LPrA2来评估瘦素信号通路的抑制对免疫缺陷小鼠所承载的人雌激素受体阳性（ER +）和雌激素受体阴性（ER -）乳腺癌异种移植物中促血管生成和促增殖分子的表达以及生长是否有不同影响。
为了测试瘦素信号通路对乳腺癌生长以及瘦素靶向分子表达的作用，对承载已建立的ER +（MCF - 7细胞；卵巢切除/补充雌二醇）和ER -（MDA - MB231细胞）乳腺癌异种移植物的重度免疫缺陷小鼠进行PEG - LPrA2治疗。为了进一步评估瘦素和PEG - LPrA2对ER +和ER -乳腺癌的影响，在细胞培养中研究了VEGF和VEGFR2（蛋白质和mRNA）的表达。
PEG - LPrA2对ER +乳腺癌生长的抑制作用（>40倍）比对ER -乳腺癌（2倍）更有效，并且在ER +乳腺癌中对促血管生成（VEGF/VEGFR2、瘦素/瘦素受体OB - R以及I型白细胞介素 - 1受体）和促增殖分子（增殖细胞核抗原和细胞周期蛋白D1）的表达的抑制作用也比在ER -乳腺癌中更强。ER +乳腺癌中的小鼠肿瘤间质表达高水平的VEGF和由瘦素信号通路诱导的瘦素。瘦素上调了MCF - 7和MDA - MB231细胞中VEGF/VEGFR2的转录表达。
这些结果表明，瘦素信号通路在ER +和ER -乳腺癌的生长中都起重要作用，这与瘦素对促血管生成和促增殖分子的调节有关。这些数据为瘦素信号通路抑制作为ER +和ER -乳腺癌的一种新型治疗方法的潜在应用提供了支持。
We have shown previously that treatment with pegylated leptin peptide receptor antagonist 2 (PEG-LPrA2) reduced the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor type 2 (VEGFR2) and growth of 4T1-breast cancer (BC) in syngeneic mice. In this investigation, PEG-LPrA2 was used to evaluate whether the inhibition of leptin signaling has differential impact on the expression of pro-angiogenic and pro-proliferative molecules and growth of human estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) BC xenografts hosted by immunodeficient mice. To test the contribution of leptin signaling to BC growth and expression of leptin-targeted molecules, PEG-LPrA2 treatment was applied to severe immunodeficient mice hosting established ER+ (MCF-7 cells; ovariectomized/supplemented with estradiol) and ER- (MDA-MB231 cells) BC xenografts. To further assess leptin and PEG-LPrA2 effects on ER+ and ER- BC, the expression of VEGF and VEGFR2 (protein and mRNA) was investigated in cell cultures. PEG-LPrA2 more effectively reduced the growth of ER+ (>40-fold) than ER- BC (twofold) and expression of pro-angiogenic (VEGF/VEGFR2, leptin/leptin receptor OB-R, and IL-1 receptor type I) and pro-proliferative molecules (proliferating cell nuclear antigen and cyclin D1) in ER+ than in ER- BC. Mouse tumor stroma in ER+ BC expressed high levels of VEGF and leptin that was induced by leptin signaling. Leptin upregulated the transcriptional expression of VEGF/VEGFR2 in MCF-7 and MDA-MB231 cells. These results suggest that leptin signaling plays an important role in the growth of both ER+ and ER- BC that is associated with the leptin regulation of pro-angiogenic and pro-proliferative molecules. These data provide support for the potential use of leptin-signaling inhibition as a novel treatment for ER+ and ER- BC.
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影响因子：
6.4
作者：
Carino, Cecilia;Olawaiye, Alexander B.;Cherfils, Salandre;Serikawa, Takehiro;Lynch, Maureen P.;Rueda, Bo R.;Gonzalez, Ruben R.
通讯作者：
Gonzalez, Ruben R.
影响因子：
4.9
作者：
Cleary, MP;Grande, JP;Maihle, NJ
通讯作者：
Maihle, NJ
影响因子：
4.8
作者：
Gonzalez, RR;Rueda, BR;Leavis, PC
通讯作者：
Leavis, PC
影响因子：
4.8
作者：
Catalano, S;Mauro, L;Andó, S
通讯作者：
Andó, S
影响因子：
158.5
作者：
Calle, EE;Rodriguez, C;Thun, MJ
通讯作者：
Thun, MJ