E-/P-selectins and colon carcinoma metastasis: first in vivo evidence for their crucial role in a clinically relevant model of spontaneous metastasis formation in the lung.
E-/P-selectins and colon carcinoma metastasis: first in vivo evidence for their crucial role in a clinically relevant model of spontaneous metastasis formation in the lung.
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DOI：
10.1038/sj.bjc.6605492
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发表时间：
2010-02-02
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
内皮选择素与肿瘤细胞糖缀合物的相互作用已被证明在先前的实验中在肿瘤细胞传播中具有重要作用。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生的。产生内皮（E）和血小板（P）-选择素缺陷型严重联合免疫缺陷（scid）小鼠，并在这些小鼠和野生型scid小鼠中皮下接种人HT 29结肠癌细胞。测定了肿瘤生长、肺中自发转移形成和HT 29细胞在流动下对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scid小鼠的转移瘤数量减少了84%。在E-和P-选择素缺陷的scid小鼠中，剩余的16%的转移瘤生长在肺动脉内，而不是像野生型scid小鼠那样生长在肺泡隔中。流动实验表明，肿瘤细胞滚动和系绳上的E-和P-选择素矩阵类似于白细胞，然而，坚定的粘附主要介导的E-选择素。我们的研究结果表明，E-和P-选择素在自发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Heptopomatia凝集素（HPA）呈阳性，该凝集素在早期临床研究中鉴定了转移表型，因此这些结果具有特别的临床相关性。
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.
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DOI：
10.1073/pnas.0402088101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Koike, T;Kimura, N;Kanangi, R
通讯作者：
Kanangi, R
影响因子：
4
作者：
Konno, A;Hoshino, Y;Kawaguchi, T
通讯作者：
Kawaguchi, T
影响因子：
4
作者：
Lafferrière, J;Houle, F;Huot, J
通讯作者：
Huot, J
影响因子：
1
作者：
MITCHELL, BS;VERNON, K;SCHUMACHER, U
通讯作者：
SCHUMACHER, U
影响因子：
4
作者：
Rajan, Suja;Ye, Jianiming;Bai, Shashan;Huang, Faqing;Guo, Yan-Lin
通讯作者：
Guo, Yan-Lin