Watkins Gareth, Douglas-Jones Anthony, Bryce Richard, Mansel Robert E, Jiang Wen G
Metastasis & Angiogenesis Research Group, University Department of Surgery, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
Prostaglandins Leukot Essent Fatty Acids. 2005 Apr;72(4):267-72. doi: 10.1016/j.plefa.2004.12.003.
SPARC (secreted protein acidic and rich in cystein), also known as osteonectin and BM40, is a 32 kDa secreted glycoprotein that interacts with extracellular matrix (ECM) proteins to promote adhesion of cells from the matrix, thereby inducing a biological state conducive to cell migration. SPARC is also thought to play an important role in tissue remodelling, angiogenesis, embryonic development and tumourigenesis. The current study set out to examine both the transcript levels of SPARC and the presence of the molecule in breast cancer tissue and to demonstrate if a link existed between the levels of SPARC and the clinical outcome. Breast tumour tissues (n=120) and non-neoplastic mammary tissues (n=32) were studied. Protein levels of SPARC were assessed using immunohistochemistry. Transcript levels of SPARC were analysed using RT-PCR. The levels were correlated with nodal status, grade, prognosis and long-term survival (10 years). Transcript levels of SPARC were found to be significantly higher in tumour tissue when compared to normal background breast tissue. This fact was mirrored when comparing levels of SPARC in ductal tumours with levels in lobular and other types of tumour. A high level of SPARC was also found in Grade 3 and TNM2 and TNM4 tumours. Node-positive tumours also exhibited higher levels of SPARC than node-negative tumours . It was also noted that SPARC was present in high levels in NPI 2 and NPI 3 tumours. Over a 6 year follow-up, high levels of SPARC was seen to be significantly associated with the overall survival of the patients (P=0.0198). However, there was no significant correlation with disease-free survival. It is concluded that SPARC plays a crucial role in tumour development in breast cancer and as such has a significant bearing on patient prognosis and long-term survival.
富含半胱氨酸的酸性分泌蛋白(SPARC),也被称为骨连接蛋白和BM40,是一种32 kDa的分泌型糖蛋白,它与细胞外基质(ECM)蛋白相互作用,促进细胞与基质的黏附,从而诱导有利于细胞迁移的生物学状态。SPARC也被认为在组织重塑、血管生成、胚胎发育和肿瘤发生中发挥重要作用。本研究旨在检测SPARC的转录水平以及该分子在乳腺癌组织中的存在情况,并证明SPARC水平与临床结果之间是否存在关联。对120例乳腺肿瘤组织和32例非肿瘤性乳腺组织进行了研究。采用免疫组织化学法评估SPARC的蛋白水平。采用逆转录聚合酶链反应(RT-PCR)分析SPARC的转录水平。这些水平与淋巴结状态、分级、预后和长期生存(10年)相关。与正常乳腺组织相比,肿瘤组织中SPARC的转录水平显著更高。在比较导管肿瘤与小叶及其他类型肿瘤中SPARC水平时也反映了这一事实。在3级、TNM2和TNM4肿瘤中也发现SPARC水平较高。淋巴结阳性肿瘤的SPARC水平也高于淋巴结阴性肿瘤。还注意到在NPI 2和NPI 3肿瘤中SPARC水平较高。在6年的随访中,发现SPARC水平高与患者的总生存率显著相关(P=0.0198)。然而,与无病生存率无显著相关性。结论是,SPARC在乳腺癌的肿瘤发展中起关键作用,因此对患者的预后和长期生存有重大影响。