Moll F, Millet C, Noël D, Orsetti B, Bardin A, Katsaros D, Jorgensen C, Garcia M, Theillet C, Pujol P, François V
Max-Planck-Institut für Biochemie, Martinsried bei München, Germany.
FASEB J. 2006 Feb;20(2):240-50. doi: 10.1096/fj.05-4126com.
Ovarian cancers mostly derive from the monolayer epithelium that covers the ovary. There are currently very few molecular clues to the etiology of this cancer. Bone morphogenetic proteins (BMPs) are required for follicular development and female fertility and are expressed in the ovarian surface epithelium (OSE). We previously reported the expression of human chordin (CHRD), a BMP extracellular regulator, in the ovary. Here we show that CHRD is underexpressed in epithelium ovary cancer and epithelial cancer cell lines as compared with normal tissues and OSE, respectively. Besides, we detected BMP expression in all ovarian cell lines analyzed. To determine the functional relevance of the absence of CHRD mRNA in tumors and cancer cell lines, we studied the effects of CHRD on two cancer cell lines, BG1 and PEO14. Migratory and invasive properties were greatly reduced, whereas cell adhesion to the support was enhanced. In addition, we detected chordin (Chrd) expression in OSE of rat ovaries in a pattern similar to that of BMP4. Altogether, these results suggest that CHRD could participate in regulating BMP activity in normal OSE physiology, and that its mis-expression in OSE may facilitate cancer incidence and/or progression.
卵巢癌大多起源于覆盖卵巢的单层上皮。目前，关于这种癌症的病因，分子线索非常少。骨形态发生蛋白（BMPs）是卵泡发育和女性生育所必需的，且在卵巢表面上皮（OSE）中表达。我们之前报道过人脊索蛋白（CHRD），一种BMP细胞外调节因子，在卵巢中表达。在此我们表明，与正常组织和OSE相比，CHRD在卵巢上皮癌和上皮癌细胞系中表达不足。此外，我们在所分析的所有卵巢细胞系中检测到了BMP表达。为了确定肿瘤和癌细胞系中CHRD mRNA缺失的功能相关性，我们研究了CHRD对两种癌细胞系BG1和PEO14的影响。迁移和侵袭特性大大降低，而细胞对支持物的黏附增强。此外，我们在大鼠卵巢的OSE中检测到脊索蛋白（Chrd）的表达模式与BMP4相似。总之，这些结果表明CHRD可能参与调节正常OSE生理中的BMP活性，并且其在OSE中的错误表达可能促进癌症的发生和/或进展。
