A SYNTHETIC PEPTIDE FROM FIBRONECTIN INHIBITS EXPERIMENTAL METASTASIS OF MURINE MELANOMA-CELLS
A SYNTHETIC PEPTIDE FROM FIBRONECTIN INHIBITS EXPERIMENTAL METASTASIS OF MURINE MELANOMA-CELLS
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DOI：
10.1126/science.3726541
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发表时间：
1986-07-25
期刊：
影响因子：
56.9
通讯作者：
YAMADA, KM
中科院分区：
文献类型：
--
作者：
HUMPHRIES, MJ;OLDEN, K;YAMADA, KM
细胞和细胞外基质之间的黏附作用发生在转移的几个阶段。这种相互作用可能会被来自基质分子细胞结合区的合成肽探针所抑制。甘氨酸-精氨酸-甘氨酸-天冬氨酸-丝氨酸(Gly-Arg-Gly-Asp-Ser，GRGDS)是一个五肽序列，在细胞与纤维连接蛋白的相互作用中起关键作用。GRGDS与B16-F10小鼠黑色素瘤细胞共注射可显著抑制C57BL/6小鼠的肺集落形成。两个密切相关的控制肽，其中GRGDS序列中的特定氨基酸被转位或取代，显示出很少的活性或没有活性。GRGDS的抑制作用是剂量依赖的，无细胞毒性，并且不是由于细胞致瘤性的损害造成的。GRGDS可能通过抑制肿瘤细胞在肺部的滞留发挥作用，因为注射了多肽的放射性标记B16-F10肿瘤细胞的丢失速度比对照细胞快得多。
Adhesive interactions between cells and the extracellular matrix occur at several stages of metastasis. Such interactions might be inhibited by synthetic peptide probes derived from the cell-binding regions of matrix molecules. Gly-Arg-Gly-Asp-Ser (GRGDS) is a pentapeptide sequence that appears to be critical for cell interaction with fibronectin. Coinjection of GRGDS with B16-F10 murine melanoma cells dramatically inhibited the formation of lung colonies in C57BL/6 mice. Two closely related control peptides, in which specific amino acids within the GRGDS sequence were transposed or substituted, displayed little or no activity. Inhibition by GRGDS was dose-dependent, noncytotoxic, and did not result from an impairment of cellular tumorigenicity. GRGDS may function by inhibiting tumor cell retention in the lung since radiolabeled B16-F10 tumor cells injected with the peptide were lost at a substantially greater rate than control cells.