Sato M, Narita T, Kimura N, Zenita K, Hashimoto T, Manabe T, Kannagi R
First Department of Surgery, Nagoya City University Medical School, Japan.
Anticancer Res. 1997 Sep-Oct;17(5A):3505-11.
The vascular endothelium plays a critical role in cancer metastasis by directing circulating cancer cells into extravascular tissues and by expressing cell adhesion molecules. The authors investigated the interaction between a cell line derived from human colon cancer and cultured murine endothelial cells, in vitro, and in vivo.
Variant cell lines with high (WiDr-HA) or low (WiDr-LA) levels of cell surface sialyl Lewis(a) antigen (s-Le(a)) were isolated from the heterogeneous WiDr cells (WiDr-P) in order to characterize the biological behavior of colon cancer cells having elevated cell surface contents of s-Le(a).
A correlation was found to exist between the degree of s-Le(a) expression, and the attachment of cancer cells to activated human umbilical vein endothelial cells, or to F-2 cells isolated from murine vascular endothelial cells. The adhesion of WiDr-P and WiDr-HA to F-2 cells was inhibited by the addition of anti-s-Le(a) antibody (Ab). WiDr-P and WiDr-HA both demonstrated the capacity to metastasize to the liver, by the inoculation of cancer cells to the spleen, while WiDr-LA did not do so. The number of metastatic nodules of WiDr-HA was significantly higher than that of WiDr-P. Treatment with anti-s-Le(a) Ab inhibited the metastasis of WiDr-P and WiDr-HA to the liver, but not with anti-s-Le(x) Ab.
These findings suggest that s-Le(a) plays an important role in cell adhesion molecules, in the metastasis of colon cancer.
血管内皮通过引导循环中的癌细胞进入血管外组织并表达细胞黏附分子,在癌症转移中起关键作用。作者研究了源自人结肠癌的细胞系与培养的鼠内皮细胞在体外和体内的相互作用。
从异质性的WiDr细胞(WiDr-P)中分离出具有高(WiDr-HA)或低(WiDr-LA)水平细胞表面唾液酸化路易斯(a)抗原(s-Le(a))的变异细胞系,以表征s-Le(a)细胞表面含量升高的结肠癌细胞的生物学行为。
发现s-Le(a)表达程度与癌细胞对活化的人脐静脉内皮细胞或从小鼠血管内皮细胞分离的F-2细胞的黏附之间存在相关性。添加抗s-Le(a)抗体(Ab)可抑制WiDr-P和WiDr-HA对F-2细胞的黏附。通过将癌细胞接种到脾脏,WiDr-P和WiDr-HA均表现出转移至肝脏的能力,而WiDr-LA则没有。WiDr-HA的转移结节数量明显高于WiDr-P。用抗s-Le(a) Ab处理可抑制WiDr-P和WiDr-HA向肝脏的转移,但抗s-Le(x) Ab则无此作用。
这些发现表明s-Le(a)在结肠癌转移的细胞黏附分子中起重要作用。