Leber Mathias Felix, Efferth Thomas
University of Mainz, Mainz, Germany.
Int J Oncol. 2009 Apr;34(4):881-95. doi: 10.3892/ijo_00000214.
The main threat and the reason for most cancer deaths are not the primary neoplasias, but secondary tumors, the metastases. Drastic phenotypic and biochemical changes occur during the metamorphosis of a normal tissue cell into an invasive cancer cell. These alterations concern various areas such as growth factor signaling, cell-cell adhesion, gene expression, motility or cell shape. Cancer cells of epithelial origin can even shed their typical qualities and characteristics and adopt a mesenchymal-like phenotype. This is often referred to as an epithelial-mesenchymal transition. Various oncogenes, tumor suppressor genes and metastasis suppressor genes are known to affect the invasiveness and the metastatic potential of tumor cells. Cells of the innate and adaptive immunity, adjacent stroma cells as well as chemokines and their receptors also play a vital role in the spread of cancer cells. Furthermore, the micro-environment, vascularization and the supply with special cytokines affect the above-mentioned changes. Finally, some researchers claim that tumors consist of two types of cells - transit amplifying cells and cancer stem cells. Only the latter are thought to be able to proliferate indefinitely and thus they might be the cells that successfully spread and initially build most of the clinically relevant metastases. This review article describes some of the molecular principles which underlie those changes as well as covers some aspects of current research.
大多数癌症死亡的主要威胁和原因并非原发性肿瘤，而是继发性肿瘤，即转移瘤。在正常组织细胞转变为侵袭性癌细胞的过程中，会发生剧烈的表型和生化变化。这些改变涉及多个领域，如生长因子信号传导、细胞间粘附、基因表达、运动性或细胞形状。上皮来源的癌细胞甚至可以摆脱其典型的性质和特征，呈现间充质样表型。这通常被称为上皮-间充质转化。已知多种癌基因、肿瘤抑制基因和转移抑制基因会影响肿瘤细胞的侵袭性和转移潜能。先天免疫和适应性免疫细胞、相邻的基质细胞以及趋化因子及其受体在癌细胞扩散中也起着至关重要的作用。此外，微环境、血管生成以及特殊细胞因子的供应会影响上述变化。最后，一些研究人员声称肿瘤由两种类型的细胞组成——过渡增殖细胞和癌症干细胞。只有后者被认为能够无限增殖，因此它们可能是成功扩散并最初形成大多数临床相关转移瘤的细胞。这篇综述文章描述了这些变化背后的一些分子原理，并涵盖了当前研究的一些方面。
