Jones P A, De Clerck Y A
Cancer Metastasis Rev. 1982;1(4):289-317. doi: 10.1007/BF00124214.
The invasion of normal tissues and penetration of basement membranes by malignant cells is likely to require the active participation of hydrolytic enzymes. The four major groups of connective tissue proteins, glycoproteins, proteoglycans, collagen and elastin, vary in their quantitative distributions between different tissues. With the exception of elastin, they also vary qualitatively within each class, so that there are no 'typical' connective tissue barriers to tumor cell penetration. The matrix constituents are stabilized and organized by a variety of covalent and noncovalent interactions between the connective tissue proteins. These interactions play important roles in matrix integrity and may alter the susceptibilities of the constituents to degradative enzymes. It is likely that the complete degradation of the matrix will require the action of more than one enzyme because of differing susceptibilities to tissue proteinases. Primary and transplantable tumors produce well-characterized enzymes which may participate in invasion. These enzymes may also be involved in connective tissue turnover in other normal and pathological situations. The use of long-term tumor cell cultures has verified that tumor cells themselves are capable of producing these enzymes. However, there are many potential modulating influences operative in vivo which are absent in culture so that details of actual mechanisms and control of digestion of complex substrates are not well understood. Recent work on the degradation by tumor cells of extracellular matrices previously produced by cultured cells is likely to shed more light on pathways of tissue destruction in vivo. Experiments with tumor cell variants of defined metastatic potentials will also be useful, but invasive and metastatic abilities are not necessarily correlated. It is unlikely that simple correlations can be drawn between the production of one particular degradative enzyme by all tumor cells and the complex biological mechanisms operative during tumor invasion.
恶性细胞对正常组织的侵袭以及对基底膜的穿透可能需要水解酶的积极参与。结缔组织蛋白、糖蛋白、蛋白聚糖、胶原蛋白和弹性蛋白这四大类，在不同组织中的定量分布各不相同。除弹性蛋白外，每一类在质量上也存在差异，因此不存在肿瘤细胞穿透的“典型”结缔组织屏障。基质成分通过结缔组织蛋白之间的多种共价和非共价相互作用得以稳定和组织化。这些相互作用在基质完整性中发挥重要作用，并且可能改变成分对降解酶的敏感性。由于对组织蛋白酶的敏感性不同，基质的完全降解可能需要不止一种酶的作用。原发性和可移植性肿瘤会产生特征明确的酶，这些酶可能参与侵袭过程。这些酶也可能在其他正常和病理情况下参与结缔组织的更新。长期肿瘤细胞培养的应用证实肿瘤细胞自身能够产生这些酶。然而，体内存在许多在培养中不存在的潜在调节影响，因此复杂底物消化的实际机制和控制细节尚未得到充分理解。近期关于肿瘤细胞对先前由培养细胞产生的细胞外基质的降解研究，可能会为体内组织破坏途径提供更多线索。对具有明确转移潜能的肿瘤细胞变体进行实验也将有所帮助，但侵袭能力和转移能力不一定相关。不太可能在所有肿瘤细胞产生一种特定降解酶与肿瘤侵袭过程中起作用的复杂生物学机制之间建立简单的关联。
