Boyer B, Vallés A M, Jouanneau J, Delouvée A, Thiery J P
Laboratoire de Physiopathologie du Développement Ecole Normale Supérieure Paris, France.
Princess Takamatsu Symp. 1994;24:233-42.
Several steps during cancer progression have been distinguished on the basis of anatomo-pathological observations and experimental data. The first step, which consists of the detachment of the cancer cells from the primary tumor prior to their migration, has received much attention. Several lines of evidence have indicated that inducer molecules of tumor cell dispersion are scatter factors which are similar or identical to some growth factors. Our studies have focused on the dispersing effect of growth factors, such as acidic FGF (aFGF) on a rat bladder carcinoma cell line. These studies demonstrated that specific extracellular matrix components might contribute to the scattering effect of soluble growth factors. Additionally, our results indicated that the dispersing action of aFGF is counterbalanced by its mitogenic effect, since these two functions of aFGF cannot be observed simultaneously for the same cell. Depending on its location in the cell collective, a given cell chooses to enter mitosis or to scatter in response to aFGF. The choice between the two responses is apparently driven by molecules belonging to the transducing pathways of aFGF signaling. Finally, our data indicated that aFGF-induced tumor cell scattering leads to increased in vitro invasiveness and in vivo metastasis. Interestingly, the presence of few aFGF-producing tumor cells in a population of non-producing cells dramatically enhances the growth rate and the metastatic properties of the whole tumor, suggesting that a low proportion of highly metastatic cells in a heterogeneous cell population might modify the behavior of the tumor mass.
基于解剖病理学观察和实验数据，癌症进展过程中的几个步骤已被区分出来。第一步是癌细胞在迁移之前从原发肿瘤脱离，这一步受到了广泛关注。几条证据表明，肿瘤细胞分散的诱导分子是散射因子，它们与某些生长因子相似或相同。我们的研究集中在生长因子，如酸性成纤维细胞生长因子（aFGF）对大鼠膀胱癌细胞系的分散作用上。这些研究表明，特定的细胞外基质成分可能有助于可溶性生长因子的散射作用。此外，我们的结果表明，aFGF的分散作用被其促有丝分裂作用所抵消，因为对于同一细胞，aFGF的这两种功能不能同时观察到。根据其在细胞群体中的位置，给定的细胞会选择进入有丝分裂或响应aFGF而分散。这两种反应之间的选择显然是由属于aFGF信号转导途径的分子驱动的。最后，我们的数据表明，aFGF诱导的肿瘤细胞散射导致体外侵袭性增加和体内转移。有趣的是，在不产生aFGF的细胞群体中存在少量产生aFGF的肿瘤细胞，会显著提高整个肿瘤的生长速度和转移特性，这表明在异质细胞群体中低比例的高转移性细胞可能会改变肿瘤块的行为。
