Role of integrins and other cell adhesion molecules in tumor progression and metastasis.
Role of integrins and other cell adhesion molecules in tumor progression and metastasis.
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发表时间：
1993
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通讯作者：
S. Albelda
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作者：
S. Albelda
尽管我们对细胞粘附生物学的理解取得了快速进展，但文献中的数据使得很难提出一个简单的方案，其中细胞粘附分子与肿瘤生长和转移有关。这种困难可能与许多因素有关。一些明显相互矛盾的实验结果表明，在肿瘤进展过程中增强或减少肿瘤细胞粘附可能归因于所使用的实验系统。一般来说，静脉注射肿瘤细胞的那些研究表明，增强的肿瘤细胞增殖与转移能力相关。应该认识到，这种实验方法绕过了许多早期阶段的转移级联反应，并偏向于具有增强的与循环中的细胞形成聚集体并粘附到远处血管部位的能力的肿瘤细胞。另一方面，将肿瘤植入动物体内并使其生长和转移（自发转移）的研究通常表明粘附能力与转移能力之间存在反比关系。理解CAM在转移中的作用的另一个主要障碍是众所周知的肿瘤异质性问题和转移细胞在相对短的时间内的表型不稳定性（141）。因此，构成转移灶的细胞可能与最初形成病变的肿瘤细胞完全不同。很有可能，最初使癌细胞形成转移性病变的选择性压力可能与后来有利于组织快速生长的压力完全不同。然而，对细胞粘附分子和肿瘤进展进行任何全面概括的主要障碍是，成功转移的过程本质上是复杂的，需要肿瘤细胞在级联中的某些点具有与周围细胞和细胞外基质的粘附相互作用降低，而在其他时间具有增加的粘附相互作用。根据现有信息，可以提出以下场景。使用图1所示的模式，成功的转移最初需要破坏正常的细胞-细胞和细胞-基质粘附，导致肿瘤细胞从原发性肿瘤释放（步骤1）。对于上皮肿瘤，下调钙粘蛋白，也许，整合素，似乎参与。这种细胞粘附的丧失之后必须是肿瘤细胞迁移到血管系统中（步骤2），这一步骤需要有效的细胞-基质相互作用。在黑色素瘤中，这一步骤似乎需要玻连蛋白受体的表达。（400字处截断摘要）
Despite rapid advances in our understanding of the biology of cell adhesion, the data available in the literature make it is difficult to propose one simple scheme in which cell adhesion molecules can be related to tumor growth and metastasis. This difficulty can be related to a number of factors. Some of the apparently conflicting experimental results that demonstrate both enhanced or diminished tumor cell adhesion during tumor progression may be attributed to the experimental systems used. Those studies that have injected tumor cells intravenously have, in general, shown that enhanced tumor cell adhesiveness correlates with metastatic ability. It should be recognized that this experimental approach bypasses many of the early stages of the metastatic cascade and is biased towards tumor cells with an enhanced ability to form aggregates with cells in the circulation and to adhere to distant vascular sites. On the other hand, studies that have implanted tumors into animals and allowed them to grow and metastasize (spontaneous metastasis) have generally demonstrated an inverse relationship between adhesive ability and the ability to metastasize. Another major obstacle in understanding the role of CAMs in metastasis is the well known problem of tumor heterogeneity and the phenotypic instability of metastatic cells over relatively short periods of time (141). The cells that make up a metastatic focus may thus be quite different from the tumor cells that originally formed the lesion. It is quite possible that the selective pressures that initially enable a cancer cell to form a metastatic lesion may be quite different than those that later favor rapid tissue growth. The major obstacle in making any sweeping generalizations about cell adhesion molecules and tumor progression, however, is that the process of successful metastasis is inherently complex, requiring tumor cells to possess decreased adhesive interactions with surrounding cells and extracellular matrix at some points in the cascade and increased adhesive interactions at other times. Based on the information available, the following scenario can be proposed. Using the schema shown in Figure 1, successful metastasis initially requires that normal cell-cell and cell-substratum adhesion be disrupted, causing release of neoplastic cells from the primary tumor (step 1). For epithelial tumors, down-regulation of cadherins and perhaps, integrins, appear to be involved. This loss of cell adhesion must be followed by migration of tumor cells into the vascular system (step 2), a step requiring efficient cell-substratum interactions. In melanomas, this step seems to require expression of the vitronectin receptor.(ABSTRACT TRUNCATED AT 400 WORDS)