Murthy M S, Weiss B D, Miller R J, Trueheart R, Scanlon E F
Department of Surgery, Evanston Hospital, IL 60201.
Clin Exp Metastasis. 1992 Jan;10(1):39-47. doi: 10.1007/BF00163575.
We report on the inhibition of wound implantation by TA3Ha mammary carcinoma cells by Arg-Gly-Asp containing proteins and peptides using a hepatic wedge resection model. Intravenously injected TA3Ha cells rarely form tumor in the liver of syngeneic mice, but after hepatic wedge resection, 45% (107/240) of the mice develop tumors in the hepatic wound. Hepatic wound implantation is significantly (P = 0.01) inhibited by pretreating the cells with whole mouse plasma, but not with fibrinogen-depleted plasma or serum. Tumor inhibition is also achieved by pretreatment of cells with fibrinogen (P = 0.05-0.0004), fibronectin (P = 0.007) and laminin, but not by albumin. The active domain appears to be the RGDS sequence since the deca- and tetrapeptides containing RGDS inhibit wound implantation (P less than 0.05). However, the tetrapeptide Arg-Gly-Glu-Ser has no such activity. None of these agents affects ascites tumor formation by the intraperitoneally injected cells, suggesting that anchorage independent growth of cells is not affected. We propose that proteins and peptides containing RGD occupy the binding sites and prevent the cells from interacting with cell adhesion proteins in healing wounds. Proteins and/or peptides containing RGD may be useful for preventing local recurrence in postsurgical cancer patients.
我们使用肝楔形切除模型报告了含精氨酸 - 甘氨酸 - 天冬氨酸（Arg - Gly - Asp）的蛋白质和肽对TA3Ha乳腺癌细胞伤口植入的抑制作用。静脉注射的TA3Ha细胞在同基因小鼠肝脏中很少形成肿瘤，但在肝楔形切除后，45%（107/240）的小鼠在肝伤口处发生肿瘤。用全小鼠血浆预处理细胞可显著（P = 0.01）抑制肝伤口植入，但用纤维蛋白原缺失的血浆或血清预处理则无此作用。用纤维蛋白原（P = 0.05 - 0.0004）、纤连蛋白（P = 0.007）和层粘连蛋白预处理细胞也可实现肿瘤抑制，但白蛋白无此作用。活性结构域似乎是RGDS序列，因为含RGDS的十肽和四肽可抑制伤口植入（P < 0.05）。然而，四肽精氨酸 - 甘氨酸 - 谷氨酸 - 丝氨酸没有这种活性。这些试剂均不影响腹腔注射细胞形成腹水肿瘤，这表明细胞的非锚定依赖性生长不受影响。我们提出，含RGD的蛋白质和肽占据了结合位点，阻止细胞与愈合伤口中的细胞粘附蛋白相互作用。含RGD的蛋白质和/或肽可能有助于预防癌症患者术后的局部复发。
