Expression and action of kit ligand/stem cell factor in normal human and bovine ovarian surface epithelium and ovarian cancer
Expression and action of kit ligand/stem cell factor in normal human and bovine ovarian surface epithelium and ovarian cancer
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DOI：
10.1095/biolreprod62.6.1600
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发表时间：
2000-06-01
影响因子：
3.6
通讯作者：
Skinner, MK
中科院分区：
文献类型：
--
作者：
Parrott, JA;Kim, G;Skinner, MK
超过 95% 的卵巢癌起源于卵巢表面的上皮细胞，称为卵巢表面上皮 (OSE)。 OSE 功能的一个正常方面是排卵后重复增殖，并且推测这在一定程度上参与了卵巢癌的发病。测试的假设是本地产生的生长因子在控制 OSE 增殖中具有重要作用。目前的研究探讨了生长因子试剂盒配体 (KL)/干细胞生长因子及其受体 c-kif 在正常 OSE 生物学和卵巢癌中的潜在作用。通过 ICC 分析，发现来自交界性、I 期和 III 期卵巢癌病例的人类肿瘤的上皮细胞成分表达 KL 和 c-kif 蛋白。人卵巢肿瘤的基质细胞成分几乎不含免疫染色。牛卵巢生理学和内分泌学与人类相似，因此牛卵巢被用作研究正常 OSE 功能的模型系统。在正常人和牛卵巢的 OSE 中检测到 KL 和 c-kit 蛋白。邻近的卵巢基质组织含有强度较低但呈阳性的 KL 和 c-kif 免疫染色。为了扩展 ICC 结果，从正常牛 OSE 和卵巢基质细胞中收集 RNA 以检查 KL 基因表达。通过 Northern 印迹分析在培养的 OSE 和基质细胞中检测到 KL 转录本。使用定量聚合酶链式反应程序发现，KL 基因表达在新鲜分离的 OSE 中较高，但在新鲜分离的基质中较低。培养的 OSE 和基质中 KL 基因表达水平增加至高水平。观察表明，正常 OSE 在体内和体外表达高水平的 KL。研究了 KL 对正常 OSE 细胞和卵巢癌细胞生长的作用。研究发现 KL 能够以与表皮生长因子类似的方式刺激正常 OSE 细胞的生长。观察结果表明正常 OSE 细胞和卵巢癌细胞产生 KL 并发挥作用。正常 OSE 中 KL 和 c-kit 的共表达表明 KL 可以作为 OSE 的自分泌因子。 KL 对 OSE 的局部产生和作用提供了对正常 OSE 生物学的深入了解，以及可能参与卵巢癌发生和进展的因素。
Greater than 95% of ovarian cancers originate from the epithelial cells on the surface of the ovary termed ovarian surface epithelium (OSE). A normal aspect of OSE function is repeated proliferation after ovulation, and this is postulated to be involved in part in the onset of ovarian cancer. The hypothesis tested is that locally produced growth factors have an important role in controlling OSE proliferation. The current study investigates the potential role of the growth factor kit ligand (KL)/stem cell growth factor and its receptor c-kif in normal OSE biology and ovarian cancer. Human tumors from borderline, stage I, and stage III cases of ovarian cancer were found to express KL and c-kif protein in the epithelial cell component by ICC analysis. The stromal cell component of human ovarian tumors contained little immunostaining. Bovine ovarian physiology and endocrinology are similar to the human such that cow ovaries were used as a model system to investigate normal OSE functions. KL and c-kit proteins were detected in the OSE from both normal human and bovine ovaries. Adjacent ovarian stromal tissue contained less intense but positive KL and c-kif immunostaining. To extend the ICC results, RNA was collected from normal bovine OSE and ovarian stromal cells to examine KL gene expression. KL transcripts were detected in cultured OSE and stromal cells by Northern blot analysis. KL gene expression was found to be high in freshly isolated OSE but low in freshly isolated stroma using a quantitative polymerase chain reaction procedure. Levels of KL gene expression in cultured OSE and stroma increased to high levels. Observations indicate that normal OSE expresses high levels of KL in vivo and in vitro. The actions of KL on the growth of both normal OSE cells and ovarian cancer cells was investigated. KL was found to stimulate the growth of normal OSE cells in a similar manner to epidermal growth factor. Observations demonstrate the production and action of KL by normal OSE cells and ovarian cancer cells. Coexpression of KL and c-kit by normal OSE suggests that KL can act as an autocrine factor for OSE. The local production and action of KL on OSE provides insight into normal OSE biology, and a factor that may be involved in the onset and progression of ovarian cancer.