PROTEOLYTIC-ENZYMES IN CANCER INVASION AND METASTASIS
PROTEOLYTIC-ENZYMES IN CANCER INVASION AND METASTASIS
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DOI：
10.1055/s-2007-1003570
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发表时间：
1986-10-01
影响因子：
5.7
通讯作者：
LIOTTA, LA
中科院分区：
文献类型：
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作者：
GOLDFARB, RH;LIOTTA, LA
虽然手术、化疗和放疗的治疗方式可以治愈大约50%的恶性肿瘤患者，但大多数对这些方式无效的患者死于转移的直接影响或与转移治疗相关的并发症。在诊断原发性肿瘤时，大约50%的患者已经具有亚临床隐匿的微转移性肿瘤集落，其最终扩展并导致直接解剖损害。临床上可检测到的一个特定器官的大转移灶可能确实表明最近开始的许多隐匿性微转移的存在。转移瘤的分散的解剖学沉积、其细胞亚群的异质性以及其大小和年龄的变化通常阻止手术切除并限制对全身性抗癌剂的反应。14，55，56此外，尽管常规治疗，如化疗或放疗，在某些情况下可以延缓转移性生长，但常规治疗通常会通过损害免疫反应而间接导致患者发病和死亡，从而导致感染性疾病的并发症。对癌症侵袭和转移的生物化学和分子机制的探索很可能会揭示有助于改善人类转移性疾病的诊断和治疗的见解。55，56在简要总结了侵袭性肿瘤细胞与宿主细胞外基质的相互作用后，我们将回顾一个三步假说，该假说描述了肿瘤细胞侵袭细胞外基质期间发生的生物化学过程的顺序：基质附着，基质溶解和肿瘤细胞运动。55，56本综述将强调广泛的细胞相关蛋白水解酶的作用，这些酶导致细胞外基质及其特定成分在癌症侵袭和转移的几个阶段中的局部降解。此外，肿瘤相关的蛋白水解酶和基质降解的肿瘤转移侵袭性的诊断和治疗策略的发展，以防止局部肿瘤侵袭和治疗已建立的人类微转移疾病的意义进行了讨论。
Whereas the treatment modalities of surgery, chemotherapy, and radiotherapy can cure approximately 50% of patients who develop malignant tumors, the majority of patients who fail to respond to these modalities succumb to the direct effect of the metastases or to complications associated with the treatment of metastases. 14'56 At the time of diagnosis of primary tumors, approximately 50% of patients already have subclinically occult micrometastatic tumor colonies that ultimately expand and lead to direct anatomic compromise. A large clinically detectable metastatic focus in a particular organ may indeed indicate the presence of numerous occult micrometastases of more recent initiation. The scattered anatomic deposits of metastases, the heterogeneity of their cellular subpopulations, and their size and age variations often prevent surgical removal and limit the response to systemic anticancer agents. 14, 55, 56 In addition, whereas conventional therapy, such as chemotherapy or radiotherapy, can in some instances retard metastatic growth, conventional therapy can often indirectly lead to patient morbidity and death by compromising the immune response resulting in complications of infectious disease. 56It is likely that the exploration of the biochemical and molecular mechanisms involved in cancer invasion and metastasis will reveal insights that will contribute to the improved diagnosis and therapy of established human metastatic disease. 55, 56 After a brief summary of the interaction of invasive tumor cells with host extracellular matrices, we will review a three-step hypothesis describing the sequence of biochemical processes that take place during tumor cell invasion of the extracellular matrix: matrix attachment, matrix dissolution, and tumor cell locomotion. 55, 56 This review will emphasize the role of a broad array of cell-associated proteolytic enzymes that lead to local degradation of extracellular matrices and their specific components during several phases of cancer invasion and metastasis. In addition, the significance of tumor-associated proteolytic enzymes and matrix degradation to the diagnosis of the metastatic aggressiveness of tumors and to the development of therapeutic strategies to prevent local tumor invasion and to treat established human micrometastatic disease is discussed.