Efficacy of continuously administered PEDF-derived synthetic peptides against osteosarcoma growth and metastasis.
Efficacy of continuously administered PEDF-derived synthetic peptides against osteosarcoma growth and metastasis.
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DOI：
10.1155/2012/230298
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发表时间：
2012
影响因子：
--
通讯作者：
Dass CR
中科院分区：
文献类型：
--
作者：
Broadhead ML;Choong PF;Dass CR
有效的抗血管生成色素上皮衍生因子（PEDF）已显示出对抗骨肉瘤的前景，骨肉瘤是一种起源于骨骼并转移至肺部的肿瘤。 PEDF 的神经营养、抗血管生成、抗增殖和抗转移特性归因于 PEDF 糖蛋白上的许多功能表位。 StVOrth-2（残基 78-102）和 StVOrth-3（残基 90-114）是两种基于这些功能表位的 PEDF 衍生肽。 StVOrth-2 先前已被证明可以抑制骨肉瘤细胞增殖，而 StVOrth-3 在体外可增加骨肉瘤细胞对 I 型胶原蛋白的粘附。在本文中，我们使用临床相关的自发转移骨肉瘤小鼠模型系统地、持续地评估了 StVOrth-2 和 StVOrth-3。在胫骨中建立原发性骨肉瘤后，开始用微渗泵进行 StVOrth-2 或 StVOrth-3 治疗。虽然StVOrth-2和StVOrth-3治疗似乎不会影响局部肿瘤侵袭、肿瘤坏死或凋亡，但StVOrth-2主要限制原发肿瘤的生长，而StVOrth-3则限制肺转移性疾病的负担。通过测量动物体重、血清生化和大体组织观察评估，没有肽对小鼠组织造成大体毒性。 StVOrth-2 和 StVOrth-3 在骨肉瘤原位模型中表现出的不同作用可能与它们所代表的 PEDF 糖蛋白上的功能表位有关。
The potent antiangiogenic pigment epithelium-derived factor (PEDF) has shown promise against osteosarcoma, a tumour that originates in the bone and metastasises to the lungs. Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of functional epitopes on the PEDF glycoprotein. StVOrth-2 (residues 78–102) and StVOrth-3 (residues 90–114) are two PEDF-derived peptides based on these functional epitopes. StVOrth-2 has previously been shown to inhibit osteosarcoma cell proliferation, while StVOrth-3 increased osteosarcoma cell adhesion to collagen I in vitro. In this paper, we have evaluated systemically and continuously delivered StVOrth-2 and StVOrth-3 using a clinically relevant murine model of osteosarcoma with spontaneous metastasis. Treatment with StVOrth-2 or StVOrth-3 with microosmotic pumps was initiated after primary osteosarcoma was established in the tibia. While treatment with StVOrth-2 and StVOrth-3 did not appear to affect local tumour invasion, tumour necrosis or apoptosis, StVOrth-2 predominantly restricted the growth of primary tumours, while StVOrth-3 restricted the burden of pulmonary metastatic disease. No peptide caused gross toxicity in mouse tissues as assessed by measuring weight of animals, serum biochemistry, and gross tissue observation. The differential effects exhibited by StVOrth-2 and StVOrth-3 in this orthotopic model of osteosarcoma may be related to the functional epitopes on the PEDF glycoprotein that they represent.
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