Loughran Elizabeth A, Phan Ryan C, Leonard Annemarie K, Tarwater Laura, Asem Marwa, Liu Yueying, Yang Jing, Klymenko Yuliya, Johnson Jeff, Shi Zonggao, Hilliard Tyvette S, Blumenthaler Marielle, Leevy Matthew, Ravosa Matthew J, Stack M Sharon
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA; Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN, USA; Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, USA.
Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, USA.
Cancer Lett. 2017 Dec 28;411:74-81. doi: 10.1016/j.canlet.2017.09.028. Epub 2017 Sep 28.
Ovarian cancer is the fifth leading cause of cancer deaths in U.S. women and the deadliest gynecologic malignancy. This lethality is largely due to the fact that most cases are diagnosed at metastatic stages of the disease when the prognosis is poor. Epidemiologic studies consistently demonstrate that parous women have a reduced risk of developing ovarian cancer, with a greater number of births affording greater protection; however little is known about the impact of parity on ovarian cancer metastasis. Here we report that multiparous mice are less susceptible to ovarian cancer metastasis in an age-matched syngeneic murine allograft model. Interferon pathways were found to be upregulated in healthy adipose tissue of multiparous mice, suggesting a possible mechanism for the multiparous-related protective effect against metastasis. This protective effect was found to be lost with age. Based on this work, future studies exploring therapeutic strategies which harness the multiparity-associated protective effect demonstrated here are warranted.
卵巢癌是美国女性癌症死亡的第五大主要原因，也是最致命的妇科恶性肿瘤。这种致命性很大程度上是因为大多数病例在疾病的转移阶段被诊断出来，此时预后很差。流行病学研究一致表明，经产女性患卵巢癌的风险降低，生育次数越多，保护作用越强；然而，关于生育状况对卵巢癌转移的影响知之甚少。在这里，我们报告在年龄匹配的同基因小鼠异种移植模型中，经产小鼠对卵巢癌转移的易感性较低。发现经产小鼠健康脂肪组织中的干扰素途径上调，这表明了经产相关的抗转移保护作用的一种可能机制。发现这种保护作用会随着年龄的增长而丧失。基于这项工作，未来有必要开展研究，探索利用此处所证明的经产相关保护作用的治疗策略。
