Department of Pathology, Pittsburgh VAMC and University of Pittsburgh, Pittsburgh, PA 15213, USA.
Front Biosci (Landmark Ed). 2011 Jan 1;16(3):815-37. doi: 10.2741/3722.
The most ominous stage of cancer progression is metastasis, or the dissemination of carcinoma cells from the primary site into distant organs. Metastases are often resistant to current extirpative therapies and even the newest biological agents cure only a small subset of patients. Therefore a greater understanding of tumor biology that integrates properties intrinsic to carcinomas with tissue environmental modulators of behavior is needed. In no aspect of tumor progression is this more evident than the acquisition of cell motility that is critical for both escape from the primary tumor and colonization. In this overview, we discuss how this behavior is modified by carcinoma cell phenotypic plasticity that is evidenced by reversible switching between epithelial and mesenchymal phenotypes. The presence or absence of intercellular adhesions mediate these switches and dictate the receptivity towards signals from the extracellular milieu. These signals, which include soluble growth factors, cytokines, and extracellular matrix embedded with matrikines and matricryptines will be discussed in depth. Finally, we will describe a new mode of discerning the balance between epithelioid and mesenchymal movement.
癌症进展最凶险的阶段是转移，即癌细胞从原发性肿瘤扩散到远处器官。转移通常对目前的根治性疗法具有耐药性，即使是最新的生物制剂也只能治愈一小部分患者。因此，需要更深入地了解肿瘤生物学，将肿瘤内在的固有特性与组织环境对行为的调节因子结合起来。在肿瘤进展的各个方面，这一点都比获得细胞运动性更为明显，因为细胞运动性对于从原发性肿瘤中逃逸和定植都至关重要。在本篇综述中，我们讨论了癌细胞表型可塑性如何改变这种行为，这种可塑性表现为上皮和间充质表型之间的可逆转换。细胞间黏附的存在或缺失介导了这些转换，并决定了细胞对细胞外环境信号的接受能力。我们将深入讨论这些信号，包括可溶性生长因子、细胞因子以及细胞外基质中嵌入的基质细胞衍生因子和基质细胞蛋白酶抑制剂。最后，我们将描述一种新的方法来辨别上皮样和间充质运动之间的平衡。
