Grant D S, Kibbey M C, Kinsella J L, Cid M C, Kleinman H K
Laboratory of Development Biology, National Institute of Dental Research, NIH, Bethesda, MD.
Pathol Res Pract. 1994 Oct;190(9-10):854-63. doi: 10.1016/S0344-0338(11)80989-1.
Expansion of the tumor-cell mass is dependent on both the degree of tumor vascularization and the rate of angiogenesis. Blood vessel growth is controlled, in part, by the matrix surrounding it, in particular, the basement membrane underlying the endothelium. Here we illustrate that laminin, a major component of basement membrane, has several biologically active sites that can bind to endothelial and tumor cells, and have the ability to regulate angiogenesis and tumor growth. We show that synthetic peptides at two sites in the laminin B1 chain (the RGD and YIGSR sequences) inhibit angiogenesis, whereas a third site in the A chain, designated SIK-VAV, stimulates vessel and tumor cell growth. By developing strategies that promote or inhibit the activities of these sites in laminin, we may obtain methods to inhibit angiogenesis and subsequent tumor growth.
肿瘤细胞团的扩张取决于肿瘤血管化程度和血管生成速率。血管生长部分受其周围基质控制，特别是内皮细胞下方的基底膜。在此我们表明，层粘连蛋白作为基底膜的主要成分，具有多个可与内皮细胞和肿瘤细胞结合的生物活性位点，并具有调节血管生成和肿瘤生长的能力。我们发现层粘连蛋白B1链上两个位点（RGD和YIGSR序列）的合成肽可抑制血管生成，而A链上的第三个位点，即SIK-VAV，则刺激血管和肿瘤细胞生长。通过开发促进或抑制层粘连蛋白中这些位点活性的策略，我们或许可以获得抑制血管生成及后续肿瘤生长的方法。
