Ween Miranda P, Oehler Martin K, Ricciardelli Carmela
Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, Research Centre for Reproductive Health, Robinson Institute, University of Adelaide, Adelaide, South Australia, 5000, Australia.
Research Centre for Infectious Diseases, School of Molecular Biosciences, University of Adelaide, South Australia 5005, Australia.
Int J Mol Sci. 2012;13(8):10461-10477. doi: 10.3390/ijms130810461. Epub 2012 Aug 21.
Transforming growth factor-beta-induced protein (TGFBI, also known as βig-H3 and keratoepithelin) is an extracellular matrix protein that plays a role in a wide range of physiological and pathological conditions including diabetes, corneal dystrophy and tumorigenesis. Many reports indicate that βig-H3 functions as a tumor suppressor. Loss of βig-H3 expression has been described in several cancers including ovarian cancer and promoter hypermethylation has been identified as an important mechanism for the silencing of the TGFBI gene. Our recent findings that βig-H3 is down-regulated in ovarian cancer and that high concentrations of βig-H3 can induce ovarian cancer cell death support a tumor suppressor role. However, there is also convincing data in the literature reporting a tumor-promoting role for βig-H3. We have shown βig-H3 to be abundantly expressed by peritoneal cells and increase the metastatic potential of ovarian cancer cells by promoting cell motility, invasion, and adhesion to peritoneal cells. Our findings suggest that βig-H3 has dual functions and can act both as a tumor suppressor or tumor promoter depending on the tumor microenvironment. This article reviews the current understanding of βig-H3 function in cancer cells with particular focus on ovarian cancer.
转化生长因子-β诱导蛋白（TGFBI，也称为βig-H3和角膜上皮素）是一种细胞外基质蛋白，在包括糖尿病、角膜营养不良和肿瘤发生在内的多种生理和病理状况中发挥作用。许多报告表明，βig-H3起着肿瘤抑制因子的作用。在包括卵巢癌在内的几种癌症中都描述了βig-H3表达的缺失，并且启动子高甲基化已被确定为TGFBI基因沉默的重要机制。我们最近的研究结果表明，βig-H3在卵巢癌中表达下调，并且高浓度的βig-H3可诱导卵巢癌细胞死亡，这支持了其肿瘤抑制作用。然而，文献中也有令人信服的数据报道βig-H3具有促肿瘤作用。我们已经表明，βig-H3在腹膜细胞中大量表达，并通过促进细胞运动、侵袭以及与腹膜细胞的黏附来增加卵巢癌细胞的转移潜能。我们的研究结果表明，βig-H3具有双重功能，并且根据肿瘤微环境的不同，它既可以作为肿瘤抑制因子，也可以作为肿瘤促进因子。本文综述了目前对βig-H3在癌细胞中功能的理解，尤其侧重于卵巢癌。
