Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs
Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs
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DOI：
10.1593/neo.04646
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发表时间：
2005-05-01
期刊：
影响因子：
4.8
通讯作者：
Glinsky, VV
中科院分区：
文献类型：
--
作者：
Glinskii, OV;Huxley, VH;Glinsky, VV
在这份报告中，我们挑战了一个普遍的看法，即肿瘤栓塞是一个大小有限的事件，机械逮捕，发生在第一个毛细血管床所遇到的血源性转移细胞。我们测试了这样的假设，即在没有肿瘤细胞粘附到血管壁的情况下，单独的机械截留不足以在靶器官微血管系统中阻止转移性细胞。体内转移性存款形成试验用于评估静脉内接种后滞留在选定器官和组织中的荧光标记肿瘤细胞的数量和位置。我们报告说，乳腺癌和前列腺癌细胞的显着部分逃脱逮捕在肺毛细血管床和住宿成功地在其他器官和组织。特异性靶向β-半乳糖苷介导的肿瘤-内皮细胞粘附相互作用的单克隆抗体和基于碳水化合物的化合物（抗-B-Friedenreich抗原抗体、抗-半乳糖凝集素-3抗体、修饰的柑橘果胶和乳果糖基-L-亮氨酸）抑制小鼠肺和骨中乳腺癌和前列腺癌转移性沉积物的体内形成> 90%。我们的研究结果表明，在靶器官微血管中的转移性细胞阻滞不是机械捕获的结果，而是主要由癌症相关的B-F糖抗原和β-半乳糖苷结合凝集素半乳糖凝集素3介导的细胞间粘附相互作用支持。β-半乳糖苷介导的粘附的有效阻断排除了靶器官中的恶性细胞寄宿。
In this report, we challenge a common perception that tumor embolism is a size-limited event of mechanical arrest, occurring in the first capillary bed encountered by blood-borne metastatic cells. We tested the hypothesis that mechanical entrapment alone, in the absence of tumor cell adhesion to blood vessel walls, is not sufficient for metastatic cell arrest in target organ microvasculature. The in vivo metastatic deposit formation assay was used to assess the number and location of fluorescently labeled tumor cells lodged in selected organs and tissues following intravenous inoculation. We report that a significant fraction of breast and prostate cancer cells escapes arrest in a lung capillary bed and lodges successfully in other organs and tissues. Monoclonal antibodies and carbohydrate-based compounds (anti-Thomsen-Friedenreich antigen antibody, anti-galectin-3 antibody, modified citrus pectin, and lactulosyl-L-leucine), targeting specifically beta-galactoside-mediated tumor-endothelial cell adhesive interactions, inhibited by > 90% the in vivo formation of breast and prostate carcinoma metastatic deposits in mouse lung and bones. Our results indicate that metastatic cell arrest in target organ microvessels is not a consequence of mechanical trapping, but is supported predominantly by intercellular adhesive interactions mediated by cancer-associated Thomsen-Friedenreich glycoantigen and beta-galactoside-binding lectin galectin-3. Efficient blocking of beta-galactoside-mediated adhesion precludes malignant cell lodging in target organs.