ProCell R&D Institute, ProCell Therapeutics, Inc., Seoul, Korea.
Cancer Res. 2011 Dec 1;71(23):7216-25. doi: 10.1158/0008-5472.CAN-11-2015. Epub 2011 Oct 10.
Occult metastases are a major cause of cancer mortality, even among patients undergoing curative resection. Therefore, practical strategies to target the growth and persistence of already established metastases would provide an important advance in cancer treatment. Here, we assessed the potential of protein therapy using a cell permeable NM23-H1 metastasis suppressor protein. Hydrophobic transduction domains developed from a screen of 1,500 signaling peptide sequences enhanced the uptake of the NM23 protein by cultured cells and systemic delivery to animal tissues. The cell-permeable (CP)-NM23 inhibited metastasis-associated phenotypes in tumor cell lines, blocked the establishment of lung metastases, and cleared already established pulmonary metastases, significantly prolonging the survival of tumor-bearing animals. Therefore, these results establish the potential use of cell-permeable metastasis suppressors as adjuvant therapy against disseminated cancers.
隐匿性转移是癌症死亡的主要原因，即使在接受根治性切除术的患者中也是如此。因此，针对已建立的转移灶的生长和持续存在的实用策略将为癌症治疗提供重要进展。在这里，我们评估了使用细胞通透性 NM23-H1 转移抑制蛋白进行蛋白治疗的潜力。从 1500 种信号肽序列的筛选中开发出的疏水性转导结构域增强了 NM23 蛋白在培养细胞中的摄取以及向动物组织的全身递送。细胞通透性 (CP)-NM23 抑制了肿瘤细胞系中的转移相关表型，阻断了肺转移的建立，并清除了已建立的肺转移，显著延长了荷瘤动物的存活时间。因此，这些结果确立了细胞通透性转移抑制剂作为针对播散性癌症的辅助治疗的潜在用途。
