Castronovo V, Stetler-Stevenson W G, Sobel M E, Liotta L A
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Princess Takamatsu Symp. 1991;22:319-37.
A group of coordinated cellular processes, not just one gene product, is responsible for invasion and metastasis, the most life-threatening aspect of cancer. It is now recognized that negative factors may be just as important as positive elements. Genetic changes causing an imbalance of growth regulation lead to uncontrolled proliferation necessary for both primary tumor and metastasis expansion. However, unrestrained growth does not, by itself, cause invasion and metastasis. This phenotype may require additional genetic changes. Thus, tumorigenicity and metastatic potential have both overlapping and separate features. Invasion and metastasis can be facilitated by proteins which stimulate tumor cell attachment to host cellular or extracellular matrix determinants, tumor cell proteolysis of host barriers, such as the basement membrane, tumor cell locomotion, and tumor cell colony formation in the target organ for metastasis. Facilitory proteins may act at many levels both intracellularly and extracellularly, but are counterbalanced by factors which can block their production, regulation or action. A common theme has emerged: in addition to loss of growth control, an imbalanced regulation of adhesion, proteolysis, and motility appears to be required for invasion and metastasis. Re-equilibrating the expression of the genes involved in these tumor invasion related events could potentially constitute the basis for new anti-cancer therapeutic strategies.
一组协调的细胞过程，而非单一的基因产物，是癌症最具生命威胁的方面——侵袭和转移的原因。现在人们认识到，负面因素可能与正面因素同样重要。导致生长调节失衡的基因变化会引发原发性肿瘤和转移灶扩展所必需的不受控制的增殖。然而，不受限制的生长本身并不会导致侵袭和转移。这种表型可能需要额外的基因变化。因此，致瘤性和转移潜能既有重叠的特征，也有各自独立的特征。刺激肿瘤细胞附着于宿主细胞或细胞外基质成分、肿瘤细胞对宿主屏障（如基底膜）进行蛋白水解、肿瘤细胞移动以及在转移靶器官中形成肿瘤细胞集落的蛋白质，均可促进侵袭和转移。促进性蛋白质可在细胞内和细胞外的多个层面发挥作用，但会受到能够阻断其产生、调节或作用的因素的制衡。一个共同的主题已经显现：除了生长控制丧失外，侵袭和转移似乎还需要黏附、蛋白水解和运动性的调节失衡。重新平衡这些与肿瘤侵袭相关事件中涉及的基因的表达，可能构成新的抗癌治疗策略的基础。
