Morimoto K, Satoh-Yamaguchi K, Hamaguchi A, Inoue Y, Takeuchi M, Okada M, Ikeda W, Takai Y, Imai T
1KAN Research Institute Inc., Kobe MI R&D Center, Kobe, Hyogo, Japan.
Oncogene. 2008 Jan 10;27(3):264-73. doi: 10.1038/sj.onc.1210645. Epub 2007 Jul 16.
Necl-5 is an immunoglobulin (Ig)-like molecule that was originally identified as a poliovirus receptor and is often upregulated in cancer cells. We recently found that it colocalizes with integrin alpha(v)beta(3) at the leading edges of moving cells and enhances growth factor-induced cell movement and proliferation. Upon cell-cell contact, Necl-5 is removed from the cell surface by its trans-interaction with the cell adhesion molecule nectin-3, resulting in reduced cell movement and proliferation. Here, we investigated the role of Necl-5 in the interaction of cancer cells with platelets. Necl-5 was upregulated in CT26 cells, a colon adenocarcinoma cell line. When CT26 cells were injected into the tail vein of mice, they were arrested in the pulmonary vessels by adhering to platelets and subsequently metastasized to the lungs. Overexpression of Necl-5 in CT26 cells enhanced this metastasis, while inhibition of the trans-interaction of Necl-5 with CD226 by an anti-Necl-5 monoclonal antibody reduced the metastasis. Depletion of platelets by treatment with a rabbit anti-mouse platelet serum reduced the Necl-5-enhanced metastasis in mice. Thus, the trans-interaction of upregulated Necl-5 in cancer cells with its counter-receptor in platelets, probably CD226, is critical for efficient metastasis of cancer cells to the lungs.
Necl-5是一种免疫球蛋白（Ig）样分子，最初被鉴定为脊髓灰质炎病毒受体，且在癌细胞中常上调表达。我们最近发现，它在移动细胞的前沿与整合素α(v)β(3)共定位，并增强生长因子诱导的细胞移动和增殖。细胞间接触时，Necl-5通过与细胞粘附分子nectin-3的反式相互作用从细胞表面被移除，导致细胞移动和增殖减少。在此，我们研究了Necl-5在癌细胞与血小板相互作用中的作用。Necl-5在结肠腺癌细胞系CT26细胞中上调表达。当将CT26细胞注射到小鼠尾静脉中时，它们通过粘附血小板而滞留在肺血管中，随后转移至肺部。CT26细胞中Necl-5的过表达增强了这种转移，而抗Necl-5单克隆抗体抑制Necl-5与CD226的反式相互作用则减少了转移。用兔抗小鼠血小板血清处理使血小板耗竭，减少了小鼠中Necl-5增强的转移。因此，癌细胞中上调的Necl-5与其血小板中的反受体（可能是CD226）的反式相互作用对于癌细胞向肺部的有效转移至关重要。
