Department of Obstetrics and Gynaecology, University of Otago, Christchurch, Christchurch, New Zealand.
Gynecol Oncol. 2012 Apr;125(1):214-9. doi: 10.1016/j.ygyno.2011.12.429. Epub 2011 Dec 16.
Endometrial cancer, in developed countries, is the most common malignancy of the female genital tract. Surgery and radiotherapy are successful in many patients but systemic and recurrent diseases have no consistently effective treatments, and for high grade advanced disease the prognosis is poor. The study investigated characteristics of adrenomedullin in endometrial cancer to assist in identifying targets for developing treatments.
Endometrial samples of women with and without cancer, and the Ishikawa cell line were used to investigate adrenomedullin mRNA regulation, peptide expression, adrenomedullin secretion and effects of adrenomedullin on VEGF secretion.
Expression of adrenomedullin mRNA was upregulated compared to that in healthy post-menopausal endometria. Adrenomedullin secretion was increased by cobalt chloride in this study. Secretion was reduced by the naturally-occurring compounds, (-)-epigallocatechin gallate (EGCG) and 3,4',5-trihydroxystilbene (resveratrol), which we have previously demonstrated to also suppress VEGF secretion in endometrial tumour tissue. We noted, for the first time, that adrenomedullin enhanced VEGF secretion from tumour cells.
Increased adrenomedullin expression may result in amplifying both tumorigenic and angiogenic activities. A substantial impact on growth of tumours may result in vivo as a consequence of the synergism between adrenomedullin and VEGF. Adrenomedullin, which has altered cellular characteristics in tumour compared to healthy tissue, offers an understudied target with potential to modify endometrial cancer behaviour, complementing other treatments.
在发达国家，子宫内膜癌是女性生殖道最常见的恶性肿瘤。手术和放疗在许多患者中取得了成功，但全身和复发性疾病尚无始终有效的治疗方法，对于高级别晚期疾病，预后较差。本研究调查了肾上腺髓质素在子宫内膜癌中的特征，以协助确定开发治疗方法的靶点。
使用患有和不患有癌症的女性子宫内膜样本和 Ishikawa 细胞系，研究了肾上腺髓质素 mRNA 的调节、肽表达、肾上腺髓质素的分泌以及肾上腺髓质素对 VEGF 分泌的影响。
与健康绝经后子宫内膜相比，肾上腺髓质素 mRNA 的表达上调。本研究中，钴氯化物增加了肾上腺髓质素的分泌。我们之前已经证明，天然存在的化合物（(-)-表没食子儿茶素没食子酸酯（EGCG）和 3,4',5-三羟基二苯乙烯（白藜芦醇）可减少其分泌，这两种化合物也可抑制子宫内膜肿瘤组织中 VEGF 的分泌。我们首次注意到，肾上腺髓质素可增强肿瘤细胞中 VEGF 的分泌。
肾上腺髓质素表达增加可能导致肿瘤发生和血管生成活性增强。由于肾上腺髓质素和 VEGF 之间的协同作用，其对肿瘤生长的巨大影响可能会在体内产生。与健康组织相比，肿瘤中具有改变的细胞特征的肾上腺髓质素提供了一个研究不足的靶点，具有改变子宫内膜癌行为的潜力，可补充其他治疗方法。
