Houle Christopher D, Ding Xiao-Yu, Foley Julie F, Afshari Cynthia A, Barrett J Carl, Davis Barbara J
Laboratory of Women's Health, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Gynecol Oncol. 2002 Jul;86(1):69-78. doi: 10.1006/gyno.2002.6729.
Impairment of cell adhesion plays a vital role in tumor progression. E- and N-cadherin, CD9, and KAI1 are all adhesion molecules that have been implicated in the progression of several different tumor types. To help explain the potential role these adhesion molecules have in ovarian cancer, comparisons were made between expression patterns in normal ovary and various grades of primary and metastatic epithelial ovarian cancers.
Thirty-two primary and 8 metastatic human ovarian epithelial carcinomas and 18 samples of normal ovarian tissue were examined for adhesion molecule expression using immunohistochemistry.
KAI1 and CD9 revealed an inverse relationship between tumor grade and expression levels, characterized by high expression in low-grade tumors and low expression in high-grade tumors and metastases. KAI1 and CD9 also demonstrated a shift in cellular localization from the membrane in grade 1 tumors to the cytoplasm in grade 3 tumors. N-cadherin expression showed a positive trend between expression levels and tumor grade. E-cadherin expression varied little between different tumor grades and metastases. Inclusion cysts (n = 6) and surface invaginations often strongly expressed KAI1, CD9, and E-cadherin. KAI1 expression was variable in ovarian follicles and corpora lutea depending on their stage of development.
Although sample size is limited, these findings suggest that progression of ovarian epithelial carcinomas is associated with down-regulation and altered cellular localization of KAI1 and CD9. In addition, variable KAI1 expression during follicular and luteal development suggests that it has a physiological function in the ovary. Further investigation will be needed to see if it is also regulated this way during progression of ovarian cancers.
细胞黏附功能受损在肿瘤进展过程中起着至关重要的作用。E-钙黏蛋白、N-钙黏蛋白、CD9和KAI1均为黏附分子,已被证实与多种不同类型肿瘤的进展有关。为了阐释这些黏附分子在卵巢癌中可能发挥的作用,我们对正常卵巢组织以及不同分级的原发性和转移性上皮性卵巢癌中的表达模式进行了比较。
采用免疫组织化学方法检测了32例原发性和8例转移性人卵巢上皮癌以及18例正常卵巢组织样本中的黏附分子表达情况。
KAI1和CD9在肿瘤分级与表达水平之间呈现出负相关关系,其特征为在低级别肿瘤中高表达,而在高级别肿瘤及转移灶中低表达。KAI1和CD9还表现出细胞定位从1级肿瘤中的细胞膜向3级肿瘤中的细胞质的转变。N-钙黏蛋白表达水平与肿瘤分级之间呈正相关趋势。不同肿瘤分级及转移灶之间E-钙黏蛋白表达变化不大。包涵囊肿(n = 6)和表面内陷常常强烈表达KAI1、CD9和E-钙黏蛋白。KAI1在卵巢卵泡和黄体中的表达因发育阶段而异。
尽管样本量有限,但这些研究结果表明,卵巢上皮癌的进展与KAI1和CD9的下调及细胞定位改变有关。此外,卵泡和黄体发育过程中KAI1表达的变化表明其在卵巢中具有生理功能。在卵巢癌进展过程中其是否也以这种方式受到调控,还需要进一步研究。