Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium.
Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium.
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DOI：
10.1016/j.urolonc.2003.12.009
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发表时间：
2003-07
期刊：
影响因子：
11.2
通讯作者：
V. Glinsky;G. Glinsky;O. Glinskii;V. Huxley;J. Turk;V. Mossine;S. Deutscher;K. Pienta;T. Quinn
中科院分区：
文献类型：
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作者：
V. Glinsky;G. Glinsky;O. Glinskii;V. Huxley;J. Turk;V. Mossine;S. Deutscher;K. Pienta;T. Quinn
肿瘤转移的两种主要理论，种子和土壤假说和机械捕获理论，认为肿瘤细胞与血管内皮细胞的黏附和癌细胞的聚集是转移过程中相应的关键组成部分。在这里，我们证明了在体外、体外和活体中，转移性乳腺癌细胞和前列腺癌细胞在它们与内皮细胞的主要附着部位形成了多细胞同型聚集体。我们的结果表明，转移细胞与微血管内皮细胞的异型黏附和同型聚集代表了转移级联的两个协调的后续步骤，主要由类似的分子机制介导，特别是通过肿瘤相关的Thomsen-Friedenreich糖抗原与β半乳糖苷结合蛋白Galectin-3的相互作用。除了抑制肿瘤细胞与内皮细胞的黏附和同型聚集外，使用合成的Thomsen-Friedenreich抗原掩蔽和Thomsen-Friedenreich抗原模拟化合物破坏这种细胞间通讯也会极大地影响癌细胞的克隆性生存和生长。因此，β-半乳糖苷介导的血管内异型和同型肿瘤细胞在微血管内皮细胞原发附着部位的粘附性相互作用可能在血源性肿瘤转移的早期阶段发挥重要作用。
The two major theories of cancer metastasis, the seed and soil hypothesis and the mechanical trapping theory, view tumor cell adhesion to blood vessel endothelia and cancer cell aggregation as corresponding key components of the metastatic process. Here, we demonstratein vitro,ex vivo, andin vivothat metastatic breast and prostate carcinoma cells form multicellular homotypic aggregates at the sites of their primary attachment to the endothelium. Our results suggest that metastatic cell heterotypic adhesion to the microvascular endothelium and homotypic aggregation represent two coordinated subsequent steps of the metastatic cascade mediated largely by similar molecular mechanisms, specifically by interactions of tumor-associated Thomsen-Friedenreich glycoantigen with the β-galactoside-binding protein, galectin-3. In addition to inhibiting neoplastic cell adhesion to the endothelium and homotypic aggregation, disrupting this line of intercellular communication using synthetic Thomsen-Friedenreich antigen masking and Thomsen-Friedenreich antigen mimicking compounds greatly affects cancer cell clonogenic survival and growth as well. Thus, β-galactoside-mediated intravascular heterotypic and homotypic tumor cell adhesive interactions at the sites of a primary attachment to the microvascular endothelium could play an important role during early stages of hematogenous cancer metastasis.