Miyake H, Hara I, Okamoto I, Gohji K, Yamanaka K, Arakawa S, Saya H, Kamidono S
Department of Urology, Kobe University School of Medicine, Japan.
J Urol. 1998 Oct;160(4):1562-6.
This study was designed to investigate the significance of the interaction between CD44 and hyaluronic acid in the development of human prostate cancer.
We transfected the standard CD44 isoform (CD44s) cDNA into PC3, a human prostate cancer cell line that barely expresses CD44s protein. The effects of the reintroduction of CD44s into PC3 cells on the ability to bind hyaluronic acid (HA) were analyzed by the cell adhesion assay and by the cell migration assay. The in vitro growth rate of CD44s transfected PC3 was measured by using the MTT assay. We then evaluated the in vivo tumor development of CD44s transfected PC3 cells by subcutaneous, intravenous, and intraperitoneal injection models in athymic nude mice.
The introduction of CD44s in PC3 cells markedly enhanced the binding and migration of these cells to HA, but not to other extracellular matrix molecules. In vitro growth of CD44s-transfected PC3 was found to be significantly decreased. In addition, the CD44s-transfected PC3 cells also demonstrated reduced tumorigenicity and metastatic potential in in vivo experimental models.
These findings suggest that the CD44s downregulation plays an important role in the development of human prostate cancer, in part through reduction of the ability to bind HA.
本研究旨在探讨CD44与透明质酸之间的相互作用在人类前列腺癌发生发展中的意义。
我们将标准CD44异构体（CD44s）cDNA转染至PC3细胞，这是一种几乎不表达CD44s蛋白的人类前列腺癌细胞系。通过细胞黏附试验和细胞迁移试验分析将CD44s重新引入PC3细胞对其结合透明质酸（HA）能力的影响。使用MTT试验测定转染CD44s的PC3细胞的体外生长速率。然后，我们通过无胸腺裸鼠的皮下、静脉和腹腔注射模型评估转染CD44s的PC3细胞的体内肿瘤发生情况。
在PC3细胞中引入CD44s显著增强了这些细胞与HA的结合和迁移能力，但与其他细胞外基质分子的结合和迁移能力未增强。发现转染CD44s的PC3细胞的体外生长显著降低。此外，在体内实验模型中，转染CD44s的PC3细胞还表现出致瘤性和转移潜能降低。
这些发现表明，CD44s下调在人类前列腺癌的发生发展中起重要作用，部分原因是其结合HA的能力降低。
