Integrin activation suppresses etoposide-induced DNA strand breakage in cultured murine tumor-derived endothelial cells.
Integrin activation suppresses etoposide-induced DNA strand breakage in cultured murine tumor-derived endothelial cells.
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发表时间：
1996-09
期刊：
影响因子：
11.2
通讯作者：
D. Hoyt;J. Rusnak;R. Mannix;R. Modzelewski;C. Johnson;J. Lazo
中科院分区：
文献类型：
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作者：
D. Hoyt;J. Rusnak;R. Mannix;R. Modzelewski;C. Johnson;J. Lazo
肿瘤内皮对实体瘤生长至关重要，并且是抗癌药物作用的潜在位点。在2小时内，依托泊苷引起显着的DNA链断裂在异种移植肿瘤衍生的内皮细胞（TDEC）。依托泊苷诱导的DNA断裂抑制培养TDEC明胶，IV型胶原蛋白，层粘连蛋白，纤连蛋白，和整合素配体六肽，GRGDSP，但不是非活性肽，GRADSP。当TDEC在用α 5、β 1或β 3整联蛋白亚基的抗体包被的表面上时，以及通过用可溶性抗体聚集整联蛋白，它也被抑制。足叶乙甙作用8 h后，TDEC从单层细胞上脱落，可见50-kb的DNA片段。纤连蛋白抑制这两个过程。因此，整合素是TDEC的存活因子，其抑制足叶乙甙的遗传毒性并可能影响肿瘤对药物的敏感性。
Tumor endothelium is critical for solid tumor growth and is a potential site for anticancer drug action. Within 2 h, etoposide caused marked DNA strand breakage in xenograft tumor-derived endothelial cells (TDECs). Etoposide-induced DNA breakage was inhibited by culturing TDECs on gelatin, type IV collagen, laminin, fibronectin, and the integrin ligand hexapeptide, GRGDSP, but not the inactive peptide, GRADSP. It was also inhibited when TDECs were on surfaces coated with antibodies to alpha 5, beta 1, or beta 3 integrin subunits and by clustering integrins with soluble antibodies. After 8 h with etoposide, TDECs detached from the monolayer, and 50-kb DNA fragments were seen. Fibronectin inhibited both processes. Thus, integrins are survival factors for TDEC that inhibit the genotoxicity of etoposide and may influence the sensitivity of tumors to drugs.