Lafrenie R M, Buchanan M R, Orr F W
Department of Pathology, McMaster University, Hamilton, Ontario.
Cell Biophys. 1993 Aug-Dec;23(1-3):3-89. doi: 10.1007/BF02796507.
This article describes various adhesion molecules and reviews evidence to support a mechanistic role for adhesion molecules in the process of cancer metastasis. A variety of evidence supports the involvement of specific adhesion molecules in metastasis. 1. For example, some cancer cells metastasize to specific organs, irrespective of the first organ encountered by the circulating cancer cells. This ability to colonize a specific organ has been correlated with the preferential adhesion of the cancer cells to endothelial cells derived from the target organ. This suggests that cancer cell/endothelial cell adhesion is involved in cancer cell metastasis and that adhesion molecules are expressed on the endothelium in an organ-specific manner. 2. Further, inclusion of peptides that inhibit cell adhesion, such as the YIGSR- or RGD-containing peptides, is capable of inhibiting experimental metastasis. 3. Metastasis can be enhanced by acute or chronic inflammation of target vessels, or by treatment of animals with inflammatory cytokines, such as interleukin-1. In vitro, cancer cell/endothelial cell adhesion can be enhanced by pretreating the endothelial cell monolayer with cytokines, such as interleukin-1 or tumor necrosis factor-alpha. This suggests that, in addition to organ-specific adhesion molecules, a population of inducible endothelial adhesion molecules is involved and is relevant to metastasis. 4. Further support for this model is found in the comparison to leukocyte/endothelial adhesion during leukocyte trafficking. Convincing evidence exists, both in vivo and in vitro, to demonstrate an absolute requirement for leukocyte/endothelial adhesion before leukocyte extravasation can occur. The relevance of this comparison to metastasis is reinforced by the observation that some of the adhesion molecules involved in leukocyte/endothelial adhesion are also implicated in cancer cell/endothelial adhesion. The involvement of adhesion molecules suggests a potential therapy for metastasis based on interrupting adhesive interactions that would augment other treatments for primary tumors.
本文描述了各种黏附分子，并综述了支持黏附分子在癌症转移过程中发挥机制作用的证据。多种证据支持特定黏附分子参与转移过程。1. 例如，一些癌细胞会转移至特定器官，而不论循环癌细胞首先遇到的是哪个器官。这种在特定器官定植的能力与癌细胞对源自靶器官的内皮细胞的优先黏附相关。这表明癌细胞/内皮细胞黏附参与癌细胞转移，且黏附分子以器官特异性方式在内皮上表达。2. 此外，包含抑制细胞黏附的肽，如含YIGSR或RGD的肽，能够抑制实验性转移。3. 靶血管的急性或慢性炎症，或用炎性细胞因子（如白细胞介素-1）治疗动物，可增强转移。在体外，用细胞因子（如白细胞介素-1或肿瘤坏死因子-α）预处理内皮细胞单层可增强癌细胞/内皮细胞黏附。这表明，除了器官特异性黏附分子外，一群可诱导的内皮黏附分子也参与其中且与转移相关。4. 与白细胞迁移过程中白细胞/内皮细胞黏附的比较进一步支持了该模型。在体内和体外都有令人信服的证据表明，在白细胞渗出发生之前，白细胞/内皮细胞黏附是绝对必要的。一些参与白细胞/内皮细胞黏附的黏附分子也与癌细胞/内皮细胞黏附有关，这一观察结果加强了这种比较与转移的相关性。黏附分子的参与提示了一种基于中断黏附相互作用的转移潜在治疗方法，这将增强对原发性肿瘤的其他治疗。
