Thomas R, True L D, Bassuk J A, Lange P H, Vessella R L
Department of Urology, University of Washington, Seattle 98195, USA.
Clin Cancer Res. 2000 Mar;6(3):1140-9.
The precise mechanism(s) involved in invasion and metastasis of prostate cancer (CaP) is poorly understood. Osteonectin [ON (also known as SPARC or BM-40)] is an antiadhesive protein known to be involved in cell-matrix interactions, migration, and angiogenesis. In this report, we studied the expression of ON in human prostate cell lines, primary tumors, and metastatic foci of CaP. Reverse transcription-PCR and nonradioactive in situ hybridization (ISH) techniques were used to determine ON gene expression. Immunohistochemistry was carried out using the polyclonal antibody LF37 and/or the monoclonal antibody ON-mAb. Low to moderate levels of ON mRNA and protein were observed in glandular epithelial cells of normal tissue as well as a few primary CaPs. However, high levels of ON mRNA and protein were observed in most of the CaP metastatic foci, both osseous and nonosseous. This correlated well with our findings that multiple different CaP cell lines including four CaP cell lines derived from metastases show high levels of ON gene expression. Furthermore, ISH analyses and cell-specific reverse transcription-PCR evaluation showed that both the luminal and basal cells express the ON gene. We conclude that the differential pattern of ON expression suggests that it may play an important role in the progression of CaP.
前列腺癌(CaP)侵袭和转移所涉及的精确机制目前仍知之甚少。骨连接蛋白[ON(也称为SPARC或BM - 40)]是一种抗黏附蛋白,已知其参与细胞与基质的相互作用、迁移及血管生成。在本报告中,我们研究了ON在人前列腺癌细胞系、原发性肿瘤及CaP转移灶中的表达情况。采用逆转录 - PCR和非放射性原位杂交(ISH)技术来测定ON基因的表达。使用多克隆抗体LF37和/或单克隆抗体ON - mAb进行免疫组织化学检测。在正常组织的腺上皮细胞以及一些原发性CaP中观察到低至中等水平的ON mRNA和蛋白。然而,在大多数CaP转移灶(包括骨转移和非骨转移灶)中均观察到高水平的ON mRNA和蛋白。这与我们的研究结果高度相关,即多种不同的CaP细胞系(包括四种源自转移灶的CaP细胞系)均显示出高水平的ON基因表达。此外,ISH分析和细胞特异性逆转录 - PCR评估表明,管腔细胞和基底细胞均表达ON基因。我们得出结论,ON表达的差异模式表明它可能在CaP的进展中起重要作用。