Suppression of tumor recurrence and metastasis by a combination of the PHSCN sequence and the antiangiogenic compound tetrathiomolybdate in prostate carcinoma.
Suppression of tumor recurrence and metastasis by a combination of the PHSCN sequence and the antiangiogenic compound tetrathiomolybdate in prostate carcinoma.
复制标题
通过 PHSCN 序列和抗血管生成化合物四硫代钼酸盐的组合来抑制前列腺癌中的肿瘤复发和转移。
DOI：
10.1038/sj.neo.7900258
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Merajver,SofiaD
中科院分区：
文献类型：
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作者：
vanGolen,KennethL;Bao,LiWei;Brewer,GeorgeJ;Pienta,KennethJ;Kamradt,JeffreyM;Livant,DonnaL;Merajver,SofiaD
在大鼠肿瘤模型中，用 Ac-PHSCN-NH2 肽处理可有效抑制血浆纤连蛋白介导的人 DU145 前列腺癌细胞系的侵袭。血浆纤连蛋白的PHSCN序列刺激DU145细胞的侵袭。然而，PHSCN 作为 PHSRN 介导的入侵的竞争性抑制剂。在本研究中，我们在无胸腺裸鼠模型中确定PHSCN是否可以抑制原发肿瘤切除后DU145肿瘤的复发和转移。我们证明，每周三次静脉注射 Ac-PHSCN-NHZ 肽治疗的小鼠在原发性肿瘤切除后可无肿瘤存活 30 周以上，而未经治疗的小鼠则在更短的时间内死于复发和/或转移性疾病。由于实体瘤生长对血管生成的普遍要求，我们测试了四硫代钼酸盐诱导的铜缺乏的功效。 (TM) 延缓邓宁前列腺癌模型中的肿瘤生长。在缺铜的小鼠中观察到原发肿瘤的大小显着减小。我们试图通过将抗侵袭 Ac-PHSCN-NH2 肽与 TM 相结合来减少原发部位和转移部位的肿瘤生长。联合治疗观察到生存率提高、转移病灶减少、耐受性良好。
Plasma fibronectin-mediated invasion of human DU145 prostate cancer cell line was efficaciously inhibited in a rat tumor model by treatment with Ac-PHSCN-NH2 peptide. Invasion of DU145 cells was stimulated by the PHSCN sequence of plasma fibronectin. However, PHSCN acts as a competitive inhibitor of PHSRNmediated invasion. In the current study, we determined whether PHSCN could inhibit the recurrence and metastasis of DU145 tumors after excision of the primary tumor in an athymic nude mouse model. We demonstrated that mice treated thrice weekly with intravenous Ac-PHSCN-NHZ peptide survived tumor-free for more than 30 weeks post-primary tumor excision, whereas their untreated counterparts succumbed to recurrence and/or metastatic disease in significantly less time. Because of the universal requirement for angiogenesis in solid tumor growth, we tested the efficacy of copper deficiency induced by tetrathiomolybdate. (TM) to retard tumor growth in the Dunning prostate cancer model. Significant reduction in size of the primary tumor was observed in mice rendered copper deficient. We sought to reduce tumor growth at the primary and metastatic sites by combining the anti-invasion Ac-PHSCN-NH2peptide with TM. Improved survival, fewer metastatic lesions, excellent tolerability were observed with the combination therapy.