Effects of Epidermal Growth Factor on Invasiveness through the Extracellular Matrix in high-and Low-metastatic Clones of Murine sarcoma.

我们研究了肿瘤细胞通过细胞外基质的侵袭性和表皮生长因子（EGF）对肿瘤细胞侵袭的影响作用，使用体外系统在C3 H/He小鼠低分化小鼠RCT肉瘤中建立的高[RCT（+）]和低转移[RCT（-）]克隆中进行。在侵袭试验中，RCT（+）细胞比RCT（-）细胞更具侵袭性。RCT（+）细胞与细胞外基质成分的附着和细胞对IV型胶原的降解显著大于RCT（-）细胞。然而，在培养的RCT（+）和RCT（-）细胞之间，细胞向细胞外基质组分的迁移没有显著差异。这些结果表明，这些克隆细胞的不同侵袭性与其粘附和降解基质的能力的差异有关。我们研究了血清层粘连蛋白和IV型胶原水平与体内肺转移的相关性，使用免疫组织化学方法，检测了血清层粘连蛋白和IV型胶原水平与肺转移的相关性。 ...更多信息 小鼠肉瘤自发性肺转移模型。结果表明，随着转移灶形成的进展，血清层粘连蛋白和IV型胶原水平逐渐升高。在本研究中，我们的数据提供的证据表明，在血清中检测到的层粘连蛋白和IV型胶原的水平升高可能是由肿瘤细胞在转移级联过程中侵入基质引起的。EGF不影响RCT（-）细胞的侵袭性。在RCT（+）细胞中，EGF可通过基质胶、细胞外基质成分的粘附和IV型胶原的降解促进其侵袭，而对向基质的迁移无影响，提示EGF的促侵袭作用与促进细胞粘附和细胞外基质降解级联反应有关。我们观察到高亲和力和低亲和力EGF受体在RCT（+）和RCT（-）细胞中均有表达，且RCT（+）细胞中EGF受体的表达水平显著高于RCT（-）细胞。在RCT（+）细胞中，EGF诱导的EGF受体磷酸化和肺转移可被抗EGF受体单克隆抗体阻断，该抗体可阻断EGF与高亲和力EGF受体的结合。少

We investigated the invasiveness of tumor cells through the extracellular matrix and influential effects of epidermal growth factor (EGF) on tumor cell invasion using in vitro systems in high-[RCT(+)] and low-metastatic [RCT(-)] clones established from poorly differentiated murine RCT sarcoma in C3H/He mice. In the invasion assay, RCT(+) cells were more invasive than RCT(-) cells. The attachment of RCT(+) cells to extracellular matrix components and the degradation of type IV collagen by the cells were significantly greater than with RCT(-) cells. However, there was no significant difference in the migration of cells to the extracellular matrix components between cultured RCT(+) and RCT(-) cells. These findings suggested that the different invasiveness of these clone cells was associated with the difference in the ability of attachment and degradation of the matrix.We investigated the correlation between serum levels of laminin and type IV collagen and pulmonary metastases in vivo, usi … More ng a murine sarcoma model of spontaneous pulmonary metastasis. The result showed that serum laminin and type IV collagen levels were found to be increased with the advance of metastasis formation. In the present study, our data provided evidence to suggest that elevated levels of laminin and type IV collagen detected in the sera might be caused by tumor cell invasion to the matrix during metastatic cascades.EGF did not affect the invasiveness of RCT(-) cells. In RCT(+) celles, EGF stimulated the invasiveness through the matrigel, the attachment to extracellular matrix components and the degradation of type IV collagen, while the migration to the matrix was not influenced by EGF.These findings suggested that the stimulatory effect of EGF on invasion is related to the acceleration of cell adhesion and the degradative cascade of the extracellular matrix in this tumor. We observed that the high- and low-affinity EGF receptors were expressed in both RCT(+) and RCT(-) cells, and the level of EGF receptor expression in RCT(+) cells was significantly higher than that in RCT(-) cells. In RCT(+) cells, EGF-induced phosphorylation of EGF receptor and pulmonary metastasis were inhibited by anti-EGF receptor monoclonal antibody which could block EGF binding to the high-affinity EGF receptor These findings suggested that EGF receptor activation has a functional role in the metastatic property of RCT sarcoma cells. Less