Department of Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
PLoS One. 2012;7(6):e39989. doi: 10.1371/journal.pone.0039989. Epub 2012 Jun 29.
CD97 is over-expressed in the majority of gastric adenocarcinomas and is associated with its dedifferentiation and aggressiveness. Our previous results demonstrated that out of three CD97 isoforms tested, only the small one was able to promote increased invasiveness in vitro. Based on these data we further aimed to investigate the role of CD97 small isoform in gastric cancer progression in vivo by employing the cells with a stable CD97 small isoform knock-down and an orthotopic gastric cancer mouse model. We could demonstrate that the knock down of CD97/EGF1,2,5, led to a significant decrease in the number of cells penetrating the gelatin coated membrane as compared with control cells. In the gastric cancer mouse model, both the hypodermic and the orthotopic yielded tumor masses of the CD97/EGF1,2,5kd group and were significantly smaller than the control. Metastatic tumor cell number in early metastatic regional lymph nodes on post-operative day 42 was distinctly decreased in the CD97/EGF1,2,5kd group as compared with the SGC-NS group, and was accompanied with the downregulation of CD44, VEGFR, CD31 and CD97. We concluded in this study that CD97 small isoform not only supported gastric cancer local growth, but also promoted metastatic spread in orthotopically implanted mouse model suggesting involvement of the CD97 small isoform in the preparation of (pre)metastatic niche.
CD97 在大多数胃腺癌中过表达，与去分化和侵袭性有关。我们之前的结果表明，在测试的三种 CD97 异构体中，只有小的异构体能够促进体外侵袭性增加。基于这些数据，我们进一步通过使用具有稳定 CD97 小异构体敲低的细胞和原位胃癌小鼠模型，旨在研究 CD97 小异构体在体内胃癌进展中的作用。我们可以证明，与对照细胞相比，CD97/EGF1,2,5 的敲低导致穿透明胶涂层膜的细胞数量显著减少。在胃癌小鼠模型中，皮下和原位肿瘤的 CD97/EGF1,2,5kd 组的肿瘤体积均明显小于对照组。与 SGC-NS 组相比，CD97/EGF1,2,5kd 组术后第 42 天早期转移区域淋巴结中的转移肿瘤细胞数量明显减少，同时伴随着 CD44、VEGFR、CD31 和 CD97 的下调。我们得出结论，CD97 小异构体不仅支持胃癌的局部生长，还促进了原位植入小鼠模型中的转移扩散，提示 CD97 小异构体参与了（前）转移龛的准备。
