Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice.
Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice.
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DOI：
10.1186/1471-2407-10-325
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发表时间：
2010-06-24
期刊：
影响因子：
3.8
通讯作者：
Prévost-Blondel A
中科院分区：
文献类型：
--
作者：
El Khoury D;Destouches D;Lengagne R;Krust B;Hamma-Kourbali Y;Garcette M;Niro S;Kato M;Briand JP;Courty J;Hovanessian AG;Prévost-Blondel A
细胞表面核仁素在肿瘤生物学中的重要性最近被研究表明，核仁素的配体在肿瘤发生和血管生成中起关键作用。通过使用结合核仁素C-末端尾部的特异性拮抗剂，HB-19假肽，我们最近报道HB-19治疗显著抑制无胸腺裸鼠中已建立的人乳腺癌细胞异种移植物的进展，而没有明显的毒性。在RET转基因小鼠模型中评估HB-19治疗对黑色素瘤自发发展的体内抗肿瘤作用。在延长300天的预防性环境中用HB-19治疗10天大的RET小鼠。与此同时，HB-19作用的分子基础在来自RET小鼠皮肤结节的黑色素瘤细胞系（称为TIII）上进行了研究。HB-19治疗RET小鼠导致皮肤肿瘤发作显著延迟，大肿瘤发生延迟数月，皮肤结节频率降低，内脏转移性结节减少，同时对正常组织无毒性。此外，与相应的对照组相比，从HB-19处理的小鼠中回收的肿瘤中的微血管密度显著降低。对黑色素瘤来源的肿瘤细胞的研究表明，HB-19处理TIII细胞可以恢复接触抑制，损害锚定非依赖性生长，并降低其在小鼠中的致瘤潜力。此外，HB-19治疗导致TIII细胞和RET小鼠黑色素瘤肿瘤中编码基质金属蛋白酶2和9以及肿瘤坏死因子-α的转录物选择性下调。虽然HB-19治疗未能阻止RET小鼠中自发性黑色素瘤的发展，但它延迟了几个月的皮肤肿瘤的发作和频率，并对内脏转移产生了显着的抑制作用。因此，HB-19本身可以提供一种新的治疗剂，或作为与目前对恶性肿瘤如黑色素瘤的治疗干预相关的辅助治疗。
The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity. The in vivo antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse. HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice. Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or as an adjuvant therapy in association with current therapeutic interventions on a virulent cancer like melanoma.
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影响因子：
4.2
作者：
Barel, Monique;Hovanessian, Ara G.;Meibom, Karin;Briand, Jean-Paul;Dupuis, Marion;Charbit, Alain
通讯作者：
Charbit, Alain
影响因子：
9.2
作者：
Dumler, I;Stepanova, V;Gulba, DC
通讯作者：
Gulba, DC
影响因子：
5.8
作者：
Hoja-Lukowicz, Dorota;Przybylo, Malgorzata;Litynska, Anna
通讯作者：
Litynska, Anna
影响因子：
3.7
作者：
Hovanessian, AG;Puvion-Dutilleul, F;Krust, B
通讯作者：
Krust, B
影响因子：
8
作者：
Huang, SY;Bucana, CD;Fidler, IJ
通讯作者：
Fidler, IJ