Papo Niv, Seger Dalia, Makovitzki Arik, Kalchenko Vyacheslav, Eshhar Zelig, Degani Hadassa, Shai Yechiel
Departments of Biological Chemistry, Biological Regulation, Veterinary Resources, and Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Cancer Res. 2006 May 15;66(10):5371-8. doi: 10.1158/0008-5472.CAN-05-4569.
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 immunodeficient 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.
我们报道了一种类似宿主防御的短肽，当将其全身接种到免疫缺陷小鼠体内时，它能够靶向并抑制侵袭性和激素抵抗性原发性人类前列腺癌和乳腺癌的生长，分别预防其实验性转移和自发性转移。这些效应与肿瘤细胞坏死增加、肿瘤微血管密度总体显著降低、新形成的毛细血管管以及前列腺特异性抗原分泌（在前列腺肿瘤中）减少相关。通过使用非侵入性全身光学成像，实时观察到了源自稳定转染的高荧光人类乳腺癌细胞的原位肿瘤的生长抑制及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预防各种癌症转移的治疗手段。
