Binding of ovarian cancer cells to peritoneal mesothelium in vitro is partly mediated by CD44H.
Binding of ovarian cancer cells to peritoneal mesothelium in vitro is partly mediated by CD44H.
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发表时间：
1993-08
期刊：
影响因子：
11.2
通讯作者：
Stephen A. Cannistra;G. Kansas;J. Niloff;B. DeFranzo;Young Ho Kim;Christian H. Ottensmeier
中科院分区：
文献类型：
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作者：
Stephen A. Cannistra;G. Kansas;J. Niloff;B. DeFranzo;Young Ho Kim;Christian H. Ottensmeier
卵巢的上皮癌通过将肿瘤细胞植入到腹膜腔的间皮内膜上扩散。我们使用正常腹膜间皮细胞的汇合单层开发了一种体外结合测定，以评估已知粘附蛋白在此过程中的作用。来自正常卵巢表面上皮和卵巢癌细胞系CAOV-3和SKOV-3的细胞表现出对间皮的显着粘附（范围为33-56％的特异性结合）。尽管这些细胞表达了几种粘附分子，包括CD44和整联蛋白，例如Alpha 4 beta 1，Alpha 5β1和Alpha Vβ3，但只有抗CD44抗体能够抑制间皮结合（范围42-44％抑制）。还确定了新鲜卵巢标本的粘附分子表达，CD44在2例正常卵巢上皮的病例中表达，16例（94％）组织衍生的肿瘤（94％）（94％）（来自原发性部位或腹膜植入物），只有2例来自腹水的自由浮动肿瘤细胞的8例（25％）。源自腹膜植入物的三个CD44阳性病例中有三个表现出显着的间皮结合，部分被抗CD44抗体阻塞，而2个CD44阴性病例中有2例来自腹水的2例表现出最小的结合。 CD44介导的卵巢癌细胞的结合被确定是由于识别间皮相关的透明质酸盐，这表明CD44H同工型参与了这一过程。卵巢癌细胞表达的CD44物种的免疫沉淀显示了2个主要条带，当时为85-90和180 kDa，与已知的CD44H分子质量一致。这些结果表明，CD44H可能是卵巢癌细胞植入的重要介质，并且在腹水形成期间，CD44H表达降低可能与细胞释放到腹膜空间有关。干扰CD44H功能的策略可能导致这种高度致命的肿瘤的腹腔内扩散减少。
Epithelial cancer of the ovary spreads by implantation of tumor cells onto the mesothelial lining of the peritoneal cavity. We have developed an in vitro binding assay using confluent monolayers of normal peritoneal mesothelial cells in order to assess the role of known adhesion proteins in this process. Cells from normal ovarian surface epithelium and the ovarian cancer cell lines CAOV-3 and SKOV-3 exhibited significant adhesion to mesothelium in vitro (range 33-56% specific binding). Although these cells expressed several adhesion molecules, including CD44 and integrins such as alpha 4 beta 1, alpha 5 beta 1, and alpha v beta 3, only anti-CD44 antibody was capable of inhibiting mesothelial binding (range 42-44% inhibition). Adhesion molecule expression was also determined for fresh ovarian specimens, with CD44 being expressed in 2 of 2 cases of normal ovarian epithelium, 15 of 16 (94%) cases of tissue-derived tumor (from primary sites or peritoneal implants), and only 2 of 8 (25%) cases of free-floating tumor cells from ascites. Three of three CD44-positive cases derived from peritoneal implants exhibited significant mesothelial binding which was partly blocked by anti-CD44 antibody, whereas 2 of 2 CD44-negative cases derived from ascites showed minimal binding. CD44-mediated binding of ovarian cancer cells was determined to be due to recognition of mesothelium-associated hyaluronate, suggesting that the CD44H isoform was involved in this process. Immunoprecipitation of the CD44 species expressed by ovarian cancer cells revealed 2 major bands at 85-90 and 180 kDa, consistent with the known molecular masses of CD44H. These results suggest that CD44H may be an important mediator of ovarian cancer cell implantation and that decreased CD44H expression may be associated with release of cells into the peritoneal space during ascites formation. It is possible that strategies to interfere with CD44H function may result in decreased intraabdominal spread of this highly lethal neoplasm.