Inhibition of tumor growth and elimination of multiple metastases in human prostate and breast xenografts by systemic inoculation of a host defense-like lytic peptide
Inhibition of tumor growth and elimination of multiple metastases in human prostate and breast xenografts by systemic inoculation of a host defense-like lytic peptide
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DOI：
10.1158/0008-5472.can-05-4569
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发表时间：
2006-05-15
期刊：
影响因子：
11.2
通讯作者：
Shai, Yechiel
中科院分区：
文献类型：
--
作者：
Papo, Niv;Seger, Dalia;Shai, Yechiel
我们报道了一种短的宿主防御样肽，当系统地接种到免疫缺陷小鼠时，它可以靶向和阻止侵袭性和激素抗性的原发性人前列腺和乳腺肿瘤的生长，并分别阻止它们的实验转移和自发转移。这些作用与肿瘤细胞坏死增加、肿瘤微血管总体密度显著降低以及新形成的毛细血管和前列腺特异性抗原分泌（在前列腺肿瘤中）相关。通过无创全身光学成像实时观察稳定转染的高荧光人乳腺癌细胞产生的原位肿瘤的生长抑制和对其自然发生转移的预防。该肽对癌症的独特选择性源于其与表面磷脂酰丝氨酸的特异性结合以及通过细胞质膜去极化杀死癌细胞。这些数据表明，膜破坏可以提供一种抑制肿瘤生长和防止各种癌症转移的治疗手段。
We report on a short host defense-like peptide that targets and arrests the growth of aggressive and hormone-resistant primary human prostate and breast tumors and prevents their experimental and spontaneous metastases, respectively, when systemically inoculated to immuodeficient mice. These effects are correlated with increased necrosis of the tumor cells and a significant decrease in the overall tumor microvessel density, as well as newly formed capillary tubes and prostate-specific antigen secretion (in prostate tumors). Growth inhibition of orthotopic tumors derived from stably transfected highly fluorescent human breast cancer cells and prevention of their naturally occurring metastases were visualized in real time by using noninvasive whole-body optical imaging. The exclusive selectivity of the peptide towards cancer derives from its specific binding to surface phosphatidylserine and the killing of the cancer cells via cytoplasmic membrane depolarization. These data indicate that membrane disruption can provide a therapeutic means of inhibiting tumor growth and preventing metastases of various cancers.