Weiss L, Ward P M
Cancer Metastasis Rev. 1983;2(2):111-27. doi: 10.1007/BF00048965.
Cancer cell detachment in three distinct and critical parts of the metastatic cascade is discussed. The detachment of cancer cells from their parent tumors is an initial early event in metastasis. The site of detachment with respect to proximity to blood vessels may determine the initial dissemination route. Many factors affect cell detachment; we specifically consider the effects of growth-rate, necrosis, enzyme activity, and stress on cell release in terms of metastasis-promoting mechanisms. Detachment is also discussed in relation to active cancer cell locomotion, where localized detachment from the substratum is a prerequisite for translatory movement. The importance of active cell movement in tissue invasion has only recently been assessed, and, in the case of at least some human malignant melanomas, a zone of actively moving cancer cells is believed to precede the growing body of the tumor. The secondary release of cancer cells from temporary arrest sites at the vascular endothelium consequent upon intravascular dissemination is also a major area of investigation. Circulating cancer cells arrest at vascular endothelium or are impacted in small vessels, however, most are released into the circulation and subsequently perish. The blood stream is a hostile environment, and it is probable that cancer cells are sufficiently damaged in translocation by hemodynamic trauma and humoral factors such that they easily detach or are 'sheared-off' the vascular endothelium by blood flow. Another possibility is that in some cases they are processed by 'first organ encounters' and perish before or shortly after arriving in a second organ. Animal studies have shown that, following intravenous injection, 60-100% of the injected dose of viable cancer cells are initially arrested in the lungs, but very few remain after 24 hr. As it is only those retained cells which produce tumors, the mechanisms involved in this secondary release, which occurs in all organs so far examined, are critical to any understanding of the metastatic cascade and metastatic inefficiency. The arrest of cancer cells at the vascular endothelium and their subsequent release have been associated with the presence of platelets, and the deposition of fibrin and manipulation of platelet-aggregating mechanisms and fibrinolysis are discussed in terms of their antimetastatic effects. The role of the reticuloendothelial system, natural killer cells, and polymorphs is discussed in relation to cancer cell clearance from blood vessels and also to inherent cancer cell properties which may act to inhibit their metastasis. Although detachment of cancer cells from a primary tumor may be regarded as metastasis promoting, secondary release of cancer cells may be associated with inhibition of metastasis.
本文讨论了转移级联反应中三个不同且关键阶段的癌细胞脱离过程。癌细胞从原发肿瘤脱离是转移过程中的一个早期起始事件。相对于血管的距离，脱离的部位可能决定了初始的播散途径。许多因素会影响细胞脱离；我们具体从促进转移的机制方面考虑生长速率、坏死、酶活性和应激对细胞释放的影响。还讨论了脱离与活跃的癌细胞运动之间的关系，其中从基质局部脱离是平移运动的先决条件。活跃的细胞运动在组织侵袭中的重要性直到最近才得到评估，并且，至少在一些人类恶性黑色素瘤的情况下，据信在肿瘤生长主体之前存在一个活跃移动的癌细胞区域。血管内播散后癌细胞从血管内皮的临时停滞部位二次释放也是一个主要的研究领域。循环中的癌细胞会在血管内皮处停滞或被困在小血管中，然而，大多数会重新进入循环并随后死亡。血流是一个恶劣的环境，癌细胞很可能在通过血流动力学创伤和体液因素进行转运时受到足够的损伤，以至于它们很容易从血管内皮脱离或被血流“剪切掉”。另一种可能性是，在某些情况下，它们会被“首次遇到的器官”处理，并在到达第二个器官之前或之后不久死亡。动物研究表明，静脉注射后，60% - 100%的注入剂量的活癌细胞最初会停滞在肺部，但24小时后很少有细胞留存。由于只有那些留存的细胞才会形成肿瘤，这种在所有已检查器官中发生的二次释放所涉及的机制，对于理解转移级联反应和转移低效性至关重要。癌细胞在血管内皮处的停滞及其随后的释放与血小板的存在有关，并且从抗转移作用方面讨论了纤维蛋白的沉积以及血小板聚集机制和纤维蛋白溶解的调控。还讨论了网状内皮系统、自然杀伤细胞和多形核细胞在清除血管中癌细胞方面的作用，以及可能抑制其转移的癌细胞固有特性。虽然癌细胞从原发肿瘤脱离可能被视为促进转移，但癌细胞的二次释放可能与转移抑制有关。
