Novel therapeutic starategy for CEACAM1 expressing colorectal cancer cells beyond the invasion front

与载体对照相比，增强的CEACAM-4S（短细胞质异构体）诱导CD44表达，增加ALDH1活性，锚定结直肠癌细胞的独立生长，提示CEACAM-4S可能诱导CSC特性。在临床环境中，CEACAM1-S（短细胞质异构体）在结直肠癌组织侵袭前沿的过度表达表明患者的生存期较差。将5FU添加到塑料上的结直肠癌细胞中，与转染CEACAM1-4S或载体对照的细胞相比，转染CEACAM1-4L的HT29细胞显著存活。在三维培养中，5FU的加入诱导CEACAM1-4S形成的大肠癌球细胞凋亡破裂。一项对III期结直肠癌患者根治性手术及辅助化疗后复发的多因素分析显示，侵袭前方外的空心球体形成是一个独立的危险因素。

Enhanced CEACAM-4S (short cytoplasmic isoform) induced CD44 expression, incresed ALDH1 activity, and anchorage indeoendent growth of colorectal cancer cells compared with vector control, suggesting that a possibility that CEACAM1-4S induce CSC property. In clinical setting, Overexpression of CEACAM1-S (short cytoplasmic isoform) at the invasion fronat of colorectal cancer tissue indicated poor survival of patients. By addition of 5FU to colorectal cancer cells on plastic, CEACAM1-4L transfected HT29 cells significantly survived in comparison with CEACAM1-4S or vector control transfected cells. In 3D culture, addition of 5FU induced apoptotic burst of colorectal cancer sphere formed by CEACAM1-4S. A multivariate analysis for recurrence after curative surgery and adjuvant chemotherapy for Stage III colorectal cancer patients showed that the hollow spheroid formation beyond the invasive front is an independent risk factor.