Paley P J, Goff B A, Gown A M, Greer B E, Sage E H
The Division of Gynecologic Oncology, University of Washington, Seattle, Washington 98195, USA.
Gynecol Oncol. 2000 Sep;78(3 Pt 1):336-41. doi: 10.1006/gyno.2000.5894.
Secreted protein, acidic and rich in cysteine (SPARC), is a matricellular protein that modulates cell adhesion and growth. It is thought to play a decisive role in tissue remodeling and angiogenesis. Alterations in SPARC expression have been observed in a variety of solid tumors; however, no consistent pattern of deregulation has been characterized. Vascular endothelial growth factor (VEGF) has emerged as an important regulator of tumor neovascularization. Recent work has shown that SPARC modulates the mitogenic activity of VEGF in normal endothelium. While its role in malignant transformation remains elusive, SPARC may contribute to tumor propagation and invasion. This study examines the immunoreactivity of SPARC and VEGF associated with neoplastic transformation of the ovary.
Immunostaining for VEGF and SPARC protein was performed on 62 archival specimens.
Fourteen normal ovaries and 48 ovarian carcinomas were evaluated. SPARC was detected in the stroma of 63% of ovarian carcinomas. In contrast, SPARC was observed in the stroma of only 29% of normal ovaries (P = 0.02). Furthermore, SPARC was limited in normal ovaries to premenopausal patients, juxtaposed either with vesiculated follicles or within the corpus luteum. VEGF was observed in 42% of ovarian carcinomas with immunoreactivity confined to tumor cells. The level of VEGF immunoreactivity was significantly higher in ovarian carcinoma compared to normal ovary epithelium (42 vs 7%, P = 0.02).
Immunoreactivity of SPARC and VEGF is heightened in association with ovarian carcinoma, with a distinct distribution of SPARC in the stroma of neoplastic ovaries and VEGF within tumor cells. No obvious pattern of coincident SPARC and VEGF immunoreactivity was detected. These results indicate the possibility of an aberration in the interaction that has been described in normal endothelium between SPARC and VEGF in association with malignant transformation.
富含半胱氨酸的酸性分泌蛋白(SPARC)是一种基质细胞蛋白,可调节细胞黏附和生长。它被认为在组织重塑和血管生成中起决定性作用。在多种实体瘤中均观察到SPARC表达的改变;然而,尚未明确其失调的一致模式。血管内皮生长因子(VEGF)已成为肿瘤新生血管形成的重要调节因子。最近的研究表明,SPARC可调节正常内皮细胞中VEGF的促有丝分裂活性。虽然其在恶性转化中的作用仍不清楚,但SPARC可能有助于肿瘤的增殖和侵袭。本研究检测与卵巢肿瘤转化相关的SPARC和VEGF的免疫反应性。
对62份存档标本进行VEGF和SPARC蛋白的免疫染色。
评估了14个正常卵巢和48例卵巢癌。63%的卵巢癌间质中可检测到SPARC。相比之下,仅29%的正常卵巢间质中观察到SPARC(P = 0.02)。此外,正常卵巢中的SPARC仅限于绝经前患者,与囊状卵泡相邻或在黄体内部。42%的卵巢癌中观察到VEGF,免疫反应性局限于肿瘤细胞。与正常卵巢上皮相比,卵巢癌中VEGF免疫反应性水平显著更高(42%对7%,P = 0.02)。
与卵巢癌相关的SPARC和VEGF免疫反应性增强,SPARC在肿瘤性卵巢间质中分布独特,VEGF在肿瘤细胞内分布独特。未检测到SPARC和VEGF免疫反应性明显一致的模式。这些结果表明,在正常内皮细胞中所描述的SPARC与VEGF之间的相互作用在恶性转化过程中可能出现异常。