Pasqualini R, Bourdoulous S, Koivunen E, Woods V L, Ruoslahti E
La Jolla Cancer Research Center, Burnham Institute, California 92037, USA.
Nat Med. 1996 Nov;2(11):1197-203. doi: 10.1038/nm1196-1197.
Metastasis accounts for most deaths in cancer patients. Tumor cell adhesion to the extracellular matrix through integrins is thought to be a critical step in metastasis and a potential target for therapeutic intervention. We show here that treatment of human osteosarcoma, melanoma and carcinoma cells with a polymeric form of fibronectin (sFN), before inoculation into nude mice, prevented tumor formation. Intraperitoneally administered sFN significantly reduced lung colonization from intravenously injected tumor cells (experimental metastasis) and from subcutaneous tumors in nude mice (spontaneous metastasis). Treatment with sFN blocked cell spreading and migration in vitro suggesting a possible mechanism for the antimetastatic effect.
转移是癌症患者死亡的主要原因。肿瘤细胞通过整合素与细胞外基质的粘附被认为是转移过程中的关键步骤,也是治疗干预的潜在靶点。我们在此表明,在将人骨肉瘤、黑色素瘤和癌细胞接种到裸鼠之前,用聚合形式的纤连蛋白(sFN)进行处理可预防肿瘤形成。腹腔注射sFN可显著减少静脉注射肿瘤细胞在肺部的定植(实验性转移)以及裸鼠皮下肿瘤的肺部定植(自发性转移)。sFN处理在体外可阻断细胞铺展和迁移,提示了其抗转移作用的可能机制。