Activation of SPARC expression in reactive stroma associated with human epithelial ovarian cancer
Activation of SPARC expression in reactive stroma associated with human epithelial ovarian cancer
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DOI：
10.1006/gyno.1999.5552
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发表时间：
1999-10-01
影响因子：
4.7
通讯作者：
Ringuette, MJ
中科院分区：
文献类型：
--
作者：
Brown, TJ;Shaw, PA;Ringuette, MJ
目标。SPARC(分泌性蛋白，酸性，富含半胱氨酸)是一种钙结合的反黏附糖蛋白，在促进肿瘤进展和侵袭方面具有重要作用。据报道，SPARC在卵巢癌中相对于正常的表面上皮显著下调，并被认为是卵巢癌中的一种肿瘤抑制因子。为了更准确地确定SPARC表达与卵巢恶性转化相关的潜在变化，我们比较了恶性和非恶性卵巢标本中SPARC基因和蛋白表达的分布。应用原位杂交和免疫组织化学方法检测24例人浸润性卵巢癌、5例低恶性潜能肿瘤和8例非恶性卵巢组织中SPARC基因和蛋白的表达。在非恶性卵巢中，SPARC基因的表达仅局限于血管卵泡的膜和颗粒细胞。SPARC免疫反应阳性细胞胞浆在这些隔室，而不同的SPARC免疫染色观察到在正常的表面上皮细胞。相反，在含有恶性肿瘤细胞的卵巢间质中检测到SPARC基因和蛋白的高水平表达，尤其是在侵袭性肿瘤的肿瘤-间质界面。低水平和更弥漫的SPARC mRNA表达模式与LMP标本相关。卵巢癌和卵巢表面上皮细胞均不表达SPARC基因。与原位杂交结果一致的是，在卵巢癌组织中，SPARC免疫反应贯穿于整个反应性间质，而尽管缺少可检测到的SPARC mRNA，但SPARC免疫反应始终存在于癌细胞的胞浆中。本研究显示SPARC的表达模式表明，SPARC在与浸润性卵巢癌相关的反应性间质中上调。此外，这些结果提出了从间质分泌的SPARC被卵巢癌细胞内化的可能性，并可能对这些细胞产生重要的细胞内效应。(C)1999年学术出版社。
Objective. SPARC (secreted protein, acidic, rich in cysteine) is a calcium-binding counteradhesive glycoprotein that has the potential to play an important role in promoting tumor progression and invasiveness. SPARC has been reported to be markedly down-regulated in ovarian carcinomas relative to the normal surface epithelium and has been suggested to act as a tumor suppressor in ovarian cancer. To more precisely define potential changes in SPARC expression associated with malignant transformation of the ovary, we compared the distribution of SPARC mRNA and protein expression in patient specimens of malignant and nonmalignant ovaries.Method. SPARC mRNA and protein expression was examined in 24 human invasive ovarian cancers, 5 tumors of low malignant potential (LMP), and 8 nonmalignant ovaries by in situ hybridization and immunohistochemistry.Results. In nonmalignant ovaries, SPARC mRNA expression was restricted to thecal and granulosa cells of vessiculated follicles. Cytoplasmic SPARC immunoreactivity was observed in these compartments, whereas variable SPARC immunostaining was observed in normal surface epithelial cells. In contrast, high-level expression of SPARC mRNA and protein was detected in stroma of ovaries containing malignant tumor cells, particularly at the tumor-stromal interface of the invading tumors. Lower levels and a more diffuse pattern of SPARC mRNA expression were associated with LMP specimens. SPARC mRNA was not expressed by ovarian adenocarcinoma or by surface epithelial cells. Consistent with the in situ hybridization data, SPARC immunoreactivity was found throughout the reactive stroma of specimens containing ovarian carcinoma, However, despite the lack of detectable SPARC mRNA, SPARC immunoreactivity was consistently observed within the cytoplasm of cancer cells.Conclusion. The pattern of SPARC expression shown in this study indicates that SPARC is up-regulated in reactive stroma associated with invasive ovarian cancer. Moreover, these results raise the possibility that SPARC secreted from the stroma is internalized by ovarian cancer cells and may exert important intracellular effects upon these cells. (C) 1999 Academic Press.