Wong Karrie, Rubenthiran Umayal, Jothy Serge
Department of Laboratory Medicine and Pathobiology, St. Michael's Hospital, and University of Toronto, Toronto, Canada.
Exp Mol Pathol. 2003 Oct;75(2):124-30. doi: 10.1016/s0014-4800(03)00053-4.
The invasion of cancer cells at primary tumor sites and their migration during metastatic spread require the expression of cell adhesion and motility proteins. Whether accelerated cell motility is necessary in these two processes is not universally accepted. In this study we took advantage that CD44, a cell adhesion protein, has different metastatic potentials depending on its splicing isoforms to examine how they affect cell motility. We established stable transfectants of standard and variant isoforms of CD44 in SW620 cells, a human colon carcinoma cell line that does not express CD44. The morphology of the cells varied according to the CD44 isoform expressed, but actin filament distribution remained unchanged. Using the wound assay in a two-dimensional in vitro cell motility system, we found that the expression of standard CD44 increases cell motility, whereas CD44 isoforms containing an exon sequence associated with metastatic dissemination has a slowing effect. Cell proliferation was also decreased by the expression of variant CD44 isoforms. Overall, colon cancer cells expressing variant CD44 isoforms had slower cell motility, possibly due to alterations in their cell adhesion properties. In conclusion, this study suggests that, contrary to common models, the metastatic phenotype is associated with a slow rate of cell migration when tested in vitro.
癌细胞在原发性肿瘤部位的侵袭及其在转移扩散过程中的迁移需要细胞粘附和运动蛋白的表达。在这两个过程中细胞运动加速是否必要，尚未得到普遍认可。在本研究中，我们利用细胞粘附蛋白CD44因其剪接异构体具有不同的转移潜能，来研究它们如何影响细胞运动。我们在SW620细胞（一种不表达CD44的人结肠癌细胞系）中建立了CD44标准异构体和变体异构体的稳定转染细胞系。细胞的形态根据所表达的CD44异构体而有所不同，但肌动蛋白丝的分布保持不变。在二维体外细胞运动系统中使用划痕试验，我们发现标准CD44的表达增加细胞运动，而含有与转移播散相关外显子序列的CD44异构体具有减缓作用。变体CD44异构体的表达也会降低细胞增殖。总体而言，表达变体CD44异构体的结肠癌细胞具有较慢的细胞运动，这可能是由于其细胞粘附特性的改变。总之，本研究表明，与常见模型相反，在体外测试时，转移表型与缓慢的细胞迁移速率相关。
