Cohen I K, Moncure C W, Witorsch R J, Diegelmann R F
Cancer Res. 1979 Aug;39(8):2923-7.
Collagen synthesis is increased over three-fold in capsules surrounding dimethylbenzanthracene-induced rat breast tumors compared to the tumor parenchyma and over six-fold compared to normal breast connective tissue. Increased collagen synthesis is independent of the rate of tumor growth and final tumor size. Pretreatment of animals with beta-aminopropionitrile to inhibit collagen cross-linking caused an 82% decrease in tumor formation and a significant reduction in tumor volume (approximately 0.4 cu cm) compared to controls (approximately 10 cu cm). The four small tumors that did develop in the lathyritic animals had increased collagen synthesis in the interior tumor stroma and reduced collagen synthesis in the tumor capsule. These findings suggest that the collagenous capsule surrounding dimethylbenzanthracene tumors functions as a physical barrier to protect the tumor from the immune system of the host. The apparent antitumor effects of beta-aminopropionitrile may be due to immunopotentiation and/or cytotoxic actions of the drug.
与肿瘤实质相比,二甲基苯并蒽诱导的大鼠乳腺肿瘤周围包膜中的胶原蛋白合成增加了三倍多,与正常乳腺结缔组织相比增加了六倍多。胶原蛋白合成的增加与肿瘤生长速度和最终肿瘤大小无关。用β-氨基丙腈预处理动物以抑制胶原蛋白交联,导致肿瘤形成减少82%,与对照组(约10立方厘米)相比,肿瘤体积显著减小(约0.4立方厘米)。在患骨生成障碍病的动物中形成的四个小肿瘤,其内部肿瘤基质中的胶原蛋白合成增加,而肿瘤包膜中的胶原蛋白合成减少。这些发现表明,二甲基苯并蒽肿瘤周围的胶原包膜起到了物理屏障的作用,保护肿瘤免受宿主免疫系统的攻击。β-氨基丙腈明显的抗肿瘤作用可能归因于该药物的免疫增强作用和/或细胞毒性作用。