Yudoh K, Matsui H, Kanamori M, Ohmori K, Yasuda T, Tsuji H
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Japan.
Tumour Biol. 1996;17(6):332-40. doi: 10.1159/000217997.
We investigated the invasiveness through the extracellular matrix and pulmonary metastatic potential in high laminin-adherent [LN(+)] and low laminin-adherent [LN(-)] Dunn oseosarcoma cells selected for adhesiveness to laminin. In the invasion assay using a reconstituted basement membrane (matrigel) in a Boyden chamber, LN(+) cells proved to be more invasive than LN(-) and the parental Dunn cells. Pulmonary metastatic potential was correlated with invasiveness through the matrigel in three cell types. The ability of LN(+) cells to attach to laminin and the matrigel was significantly higher than that of LN(-) or the parental Dunn cells. LN(-) cells showed much lower attachment ability compared to the other cells. There were no significant differences in type IV collagenolysis and cell migration among the three cell types. In LN(+) and the parental Dunn cells, laminin significantly stimulated type IV collagenolytic and migration activities. LN(-) cells showed no significant differences of type IV collagenolysis and cell migration in response to laminin. These findings suggested that the different invasiveness of these cells was associated with the difference in the abilities of cell attachment to laminin and type IV collagenolysis and cell migration activities stimulated by laminin. YIGSR inhibited not only the laminin-mediated cell attachment but also the type IV collagenolysis and cell migration induced by the cell attachment to laminin. The amount of laminin receptor of LN(+) cells was about fourfold that of LN(-) and twofold that of the parental Dunn cells, suggesting the stimulatory effect of laminin on the invasiveness through the matrix is associated with the level of laminin receptor expression in these cells. The present study provides several findings suggesting that laminin has important roles in invasiveness through the extracellular matrix and metastasis formation in Dunn osteosarcoma cells.
我们研究了从对层粘连蛋白粘附性方面筛选出的高层粘连蛋白粘附性[LN(+)]和低层粘连蛋白粘附性[LN(-)]的邓恩骨肉瘤细胞穿过细胞外基质的侵袭性及肺转移潜能。在使用博伊登小室中的重组基底膜（基质胶）进行的侵袭试验中，LN(+)细胞比LN(-)细胞及亲本邓恩细胞更具侵袭性。三种细胞类型的肺转移潜能与穿过基质胶的侵袭性相关。LN(+)细胞与层粘连蛋白和基质胶的附着能力显著高于LN(-)细胞或亲本邓恩细胞。与其他细胞相比，LN(-)细胞显示出低得多的附着能力。三种细胞类型在IV型胶原酶解和细胞迁移方面无显著差异。在LN(+)细胞和亲本邓恩细胞中，层粘连蛋白显著刺激IV型胶原酶解和迁移活性。LN(-)细胞对层粘连蛋白的反应在IV型胶原酶解和细胞迁移方面无显著差异。这些发现表明，这些细胞不同的侵袭性与细胞对层粘连蛋白的附着能力差异以及层粘连蛋白刺激的IV型胶原酶解和细胞迁移活性差异有关。YIGSR不仅抑制层粘连蛋白介导的细胞附着，还抑制细胞附着于层粘连蛋白所诱导的IV型胶原酶解和细胞迁移。LN(+)细胞中层粘连蛋白受体的量约为LN(-)细胞的四倍，亲本邓恩细胞的两倍，这表明层粘连蛋白对穿过基质的侵袭性的刺激作用与这些细胞中层粘连蛋白受体的表达水平有关。本研究提供了多项发现，表明层粘连蛋白在邓恩骨肉瘤细胞穿过细胞外基质的侵袭性及转移形成中起重要作用。
