Institute for Anatomy II: Experimental Morphology, University Cancer Center Hamburg, University Medical Center Hamburg Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Br J Cancer. 2010 Feb 2;102(3):602-9. doi: 10.1038/sj.bjc.6605492. Epub 2009 Dec 15.
Interactions of endothelial selectins with tumour cell glycoconjugates have been shown to have a major role in tumour cell dissemination in previous experiments. However, experiments validating this observation were limited in value, as 'metastases' in these experiments were artificially induced by i.v. injection rather than developed spontaneously as in true metastases.
Endothelial (E) and platelet (P)-selectin-deficient severe combined immunodeficient (scid) mice were generated and human HT 29 colon cancer cells were subcutaneously inoculated in these mice and in wild-type scid mice. Tumour growth, spontaneous metastasis formation in the lung and adherence of HT29 cells to E- and P-selectin under flow were determined.
The number of metastases decreased by 84% in E- and P-selectin-deficient scid mice, compared with wild-type scid mice. The remaining 16% metastases in the E- and P-selectin-deficient scid mice grew within the pulmonary artery and not in the alveolar septae as they did in wild-type scid mice. Flow experiments indicate that tumour cells roll and tether on an E- and P-selectin matrix similar to leukocytes; however, firm adhesion is mainly mediated in E-selectin.
Our results indicate that E- and P-selectins have a crucial role in spontaneous metastasis formation. As the human HT 29 colon cancer cells are positive for the lectin Helix pomatia agglutinin (HPA), which identified the metastatic phenotype in earlier clinical studies, these results are of particular clinical relevance.
在之前的实验中，已经证明内皮选择素与肿瘤细胞糖缀合物的相互作用在肿瘤细胞扩散中起着重要作用。然而，验证这一观察结果的实验价值有限，因为这些实验中的“转移”是通过静脉注射人为诱导的，而不是像真正的转移那样自发发展的。
生成内皮（E）和血小板（P）-选择素缺陷的严重联合免疫缺陷（scid）小鼠，并将人 HT 29 结肠癌细胞皮下接种于这些小鼠和野生型 scid 小鼠中。测定肿瘤生长、肺内自发性转移形成以及 HT29 细胞在流动条件下与 E-和 P-选择素的粘附。
与野生型 scid 小鼠相比，E-和 P-选择素缺陷型 scid 小鼠的转移数量减少了 84%。在 E-和 P-选择素缺陷型 scid 小鼠中，剩余的 16%转移发生在肺动脉内，而不是在野生型 scid 小鼠中发生在肺泡隔内。流动实验表明，肿瘤细胞类似于白细胞在 E-和 P-选择素基质上滚动和固定；然而，牢固的粘附主要由 E-选择素介导。
我们的结果表明，E-和 P-选择素在自发性转移形成中起着至关重要的作用。由于人 HT 29 结肠癌细胞对凝集素 Helix pomatia agglutinin（HPA）呈阳性，这在早期临床研究中确定了转移表型，因此这些结果具有特别的临床相关性。
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