Gao A C, Lou W, Sleeman J P, Isaacs J T
The Johns Hopkins Oncology Center, James Buchanan Brady Urological Institute, Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231-1001, USA.
Cancer Res. 1998 Jun 1;58(11):2350-2.
Previous studies from this laboratory have demonstrated that down-regulation of the standard CD44 isoform at the mRNA and protein level is associated with the acquisition of high metastatic ability within the Dunning R-3327 system of rat prostate cancers. Additional studies demonstrated that transfection-induced enhanced expression of the standard CD44 isoform suppresses the metastatic ability of the AT3.1 Dunning subline without suppressing tumorigenicity. The standard CD44 isoform is a major cell surface receptor for the extracellular matrix glycosaminoglycan hyaluronate. In this study, an investigation was made to resolve whether the ability of the standard CD44 isoform to suppress metastasis of the AT3.1 prostate cancer cells critically requires enhanced hyaluronate binding. Highly metastatic Dunning AT3.1 rat prostate cancer cells were transfected with expression plasmids encoding either the wild-type or mutant standard CD44 isoform. The mutant standard CD44 isoform construct encoded a protein unable to bind to hyaluronate. Transfectants were isolated and characterized with regard to their level of standard CD44 isoform expression, hyaluronate binding, tumorigenicity, and metastatic ability. Expression of the wild-type standard CD44 isoform increased the hyaluronate binding of prostate cancer cells and suppressed their metastatic ability without suppressing their tumorigenicity. Expression of the mutant CD44 standard isoform did not increase hyaluronate binding; however, it equally suppressed the metastatic ability of the AT3.1 prostate cancer cells. These results demonstrate that the metastasis suppression by the standard CD44 isoform is independent of its ability to bind to hyaluronate.
该实验室先前的研究表明，在大鼠前列腺癌的邓宁R-3327系统中，标准CD44异构体在mRNA和蛋白质水平的下调与高转移能力的获得有关。进一步的研究表明，转染诱导的标准CD44异构体表达增强可抑制AT3.1邓宁亚系的转移能力，而不抑制其致瘤性。标准CD44异构体是细胞外基质糖胺聚糖透明质酸的主要细胞表面受体。在本研究中，我们进行了一项调查，以确定标准CD44异构体抑制AT3.1前列腺癌细胞转移的能力是否严重依赖于增强的透明质酸结合。用编码野生型或突变型标准CD44异构体的表达质粒转染高转移性邓宁AT3.1大鼠前列腺癌细胞。突变型标准CD44异构体构建体编码一种不能与透明质酸结合的蛋白质。分离转染子，并对其标准CD44异构体表达水平、透明质酸结合、致瘤性和转移能力进行表征。野生型标准CD44异构体的表达增加了前列腺癌细胞的透明质酸结合，并抑制了它们的转移能力，而不抑制其致瘤性。突变型CD44标准异构体的表达没有增加透明质酸结合；然而，它同样抑制了AT3.1前列腺癌细胞的转移能力。这些结果表明，标准CD4异构体对转移的抑制作用与其结合透明质酸的能力无关。
