Urtreger A, Porro F, Puricelli L, Werbajh S, Baralle F E, Bal de Kier Joffé E, Kornblihtt A R, Muro A F
Institute of Oncology Angel H. Roffo, University of Buenos Aires, Argentina.
Int J Cancer. 1998 Oct 5;78(2):233-41. doi: 10.1002/(sici)1097-0215(19981005)78:2<233::aid-ijc18>3.0.co;2-b.
Fibronectin (FN) is a plasma and extracellular matrix (ECM) glycoprotein, the expression of which may modulate the invasive and metastatic abilities of cancer cells. LMM3 is a cell line derived from the highly metastatic mouse mammary adenocarcinoma MM3 and is unable to express FN both at protein and mRNA levels. To study the role of FN in the metastatic process, LMM3 cells were stably transfected with 2 variants (wt and RGD-minus) of a full length human FN cDNA. All analyzed clones secreted recombinant FN and although none assembled FN in the ECM they showed an in vitro reduced migratory ability and an increased adhesive capacity. FN-producing cells were assayed for experimental and spontaneous metastasis. All clones tested showed a significant reduction in the number of experimental lung metastasis when compared with a control clone. Similar trends were observed for spontaneous metastatic ability. Our results indicate that the expression of FN that lacks the well-recognized RGD cell-binding site and that does not form ECM fibrils, is sufficient to decrease the metastatic potential of cancer cells. Our results also suggest that an RGD-independent mechanism may be acting in the prevention of metastasis.
纤连蛋白（FN）是一种血浆和细胞外基质（ECM）糖蛋白，其表达可能会调节癌细胞的侵袭和转移能力。LMM3是一种源自高转移性小鼠乳腺腺癌MM3的细胞系，在蛋白质和mRNA水平上均无法表达FN。为了研究FN在转移过程中的作用，用全长人FN cDNA的2种变体（野生型和RGD缺失型）对LMM3细胞进行了稳定转染。所有分析的克隆均分泌重组FN，尽管没有一个在ECM中组装FN，但它们在体外显示出迁移能力降低和黏附能力增强。对产生FN的细胞进行了实验性和自发性转移检测。与对照克隆相比，所有测试的克隆在实验性肺转移数量上均显著减少。在自发性转移能力方面也观察到了类似趋势。我们的结果表明，缺乏公认的RGD细胞结合位点且不形成ECM纤维的FN的表达足以降低癌细胞的转移潜能。我们的结果还表明，一种不依赖RGD的机制可能在预防转移中起作用。
