The FGF-1-specific single-chain antibody scFv1C9 effectively inhibits breast cancer tumour growth and metastasis.
The FGF-1-specific single-chain antibody scFv1C9 effectively inhibits breast cancer tumour growth and metastasis.
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FGF-1特异性单链抗体scFv1C9可有效抑制乳腺癌肿瘤的生长和转移。
DOI：
10.1111/jcmm.12371
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发表时间：
2014-10
影响因子：
5.3
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Shi H;Fu C;Wang W;Li Y;Du S;Cao R;Chen J;Sun D;Zhang Z;Wang X;Zhu X
重组抗体介导的免疫治疗是治疗多种癌症的有效策略。在先前的研究中，我们证明了成纤维细胞生长因子1（FGF-1）特异性重组抗体scFv 1C 9通过阻断乳腺癌细胞内分泌FGF-1途径，将细胞周期阻滞在G 0/G1期。在这里，我们进一步表明，通过慢病毒感染在MCF-7和MDA-MB-231乳腺癌细胞中过表达scFv 1C 9导致通过FGF-1中和降低的致瘤性、肿瘤生长和肺转移。我们发现scFv 1C 9导致p21的上调，从而抑制CDK 2的表达并阻断细胞周期进程。为了探索scFv 1C 9在体内的潜在作用，我们通过电穿孔将该基因递送到实体瘤中，这导致了对肿瘤生长的显著抑制。在肿瘤组织切片中，细胞增殖标记物Ki-67和微血管标记物CD 31的免疫组织化学染色显示，与适当的对照相比，表达scFv 1C 9后，增殖指数和微血管密度分别降低。因此，我们的数据表明scFv 1C 9在阻断FGF-1的胞内分泌途径中的核心作用，因此，scFv 1C 9可以被开发为乳腺癌的有效治疗剂。
Immunotherapy mediated by recombinant antibodies is an effective therapeutic strategy for a variety of cancers. In a previous study, we demonstrated that the fibroblast growth factor 1 (FGF-1)-specific recombinant antibody scFv1C9 arrests the cell cycle at the G0/G1 transition by blocking the intracrine FGF-1 pathway in breast cancer cells. Here, we further show that the overexpression of scFv1C9 in MCF-7 and MDA-MB-231 breast cancer cells by lentiviral infection resulted in decreased tumourigenicity, tumour growth and lung metastasis through FGF-1 neutralization. We found that scFv1C9 resulted in the up-regulation of p21, which in turn inhibited the expression of CDK2 and blocked cell cycle progression. To explore the potential role of scFv1C9 in vivo, we delivered the gene into solid tumours by electroporation, which resulted in significant inhibition of tumour growth. In tumour tissue sections, immunohistochemical staining of the cellular proliferation marker Ki-67 and the microvessel marker CD31 showed a reduction in the proliferative index and microvessel density, respectively, upon expression of scFv1C9 compared with the appropriate controls. Thus, our data indicate a central role for scFv1C9 in blocking the intracrine pathway of FGF-1, therefore, scFv1C9 could be developed in an effective therapeutic for breast cancer.
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影响因子：
7.2
作者：
Bouleau, Sylvina;Parvu-Ferecatu, Ioana;Renaud, Flore
通讯作者：
Renaud, Flore
DOI：
10.1152/ajpendo.00089.2006
发表时间：
2007-03-01
影响因子：
5.1
作者：
Sun, Haijun D.;Malabunga, Maria;Kussie, Paul
通讯作者：
Kussie, Paul
DOI：
10.1073/pnas.97.1.354
发表时间：
2000-01-04
影响因子：
11.1
作者：
Goto, T;Nishi, T;Ushio, Y
通讯作者：
Ushio, Y
影响因子：
3.1
作者：
Chow, NH;Cheng, KS;Lin, XZ
通讯作者：
Lin, XZ
影响因子：
5.4
作者：
Dull, T;Zufferey, R;Naldini, L
通讯作者：
Naldini, L