SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells
SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells
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DOI：
10.1016/s0002-9440(10)61732-4
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发表时间：
2001-08-01
影响因子：
6
通讯作者：
Mok, SC
中科院分区：
文献类型：
--
作者：
Yiu, GK;Chan, WY;Mok, SC
富含半胱氨酸的酸性分泌蛋白(SPARC)是一种与细胞外钙离子结合的基质糖蛋白，与细胞迁移、形态发生和分化有关。对内皮细胞的研究表明，它在体外的主要功能是抗黏附和抗增殖。这些抗肿瘤作用的机制(S)尚不清楚。在这项研究中，我们发现SPARC在卵巢癌细胞中的表达与恶性程度呈负相关。本文提供的免疫组织化学数据证实了SPARC表达减弱在卵巢癌发生发展中的重要性。用SPARC处理人卵巢表面上皮细胞和卵巢癌细胞发现，由于SPARC同时抑制正常细胞和癌细胞的增殖，所以它只诱导癌细胞凋亡。这一观察表明，SPARC的下调在卵巢癌的发生中是必不可少的，因为癌细胞在恶性转化过程中对SPARC的凋亡活性变得敏感。我们还首次直接证明卵巢上皮细胞上存在可能的SPARC受体。其在人卵巢表面上皮细胞中的表达水平高于癌细胞。SPARC与其受体的结合可能触发组织特异性信号通路，介导其肿瘤抑制功能。通过下调SPARC和/或其受体来减少配体与受体的相互作用是卵巢癌发生的关键。
Secreted protein acidic and rich in cysteine (SPARC) is an extracellular Ca2+-binding matricellular glycoprotein that associates with cell populations undergoing migration, morphogenesis, and differentiation. Studies on endothelial cells have established that its principal functions in vitro are counteradhesion and antiproliferation. The mechanism(s) underlying these antitumor effects is unknown. in this study, we showed that SPARC expression in ovarian cancer cells is inversely correlated with the degree of malignancy. The immunohistochemical data presented here confirmed the importance of diminished SPARC expression in ovarian cancer development. Treating human ovarian surface epithelial cells and ovarian cancer cells with SPARC revealed that as SPARC inhibits the proliferation of both normal and cancer cells, it induces apoptosis only in cancer cells. This observation indicates that down-regulation of SPARC is essential for ovarian carcinogenesis as cancer cells become sensitized to the apoptotic activity of SPARC during malignant transformation. We also showed re the first direct evidence that putative SPARC receptors are present on ovarian epithelial cells. Their level s are higher hi human ovarian surface epithelial cells than cancer cells. Binding of SPARC to its receptor is likely to trigger tissue-specific signaling pathways that mediate its tumor suppressing functions. Decrease in ligand-receptor interaction by the down-regulation of SPARC and/or its receptor is essential for ovarian carcinogenesis.