Harper Elizabeth I, Sheedy Emma F, Stack M Sharon
Department of Chemistry and Biochemistry, University of Notre Dame, South Bend, IN 46617, USA.
Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46617, USA.
Cancers (Basel). 2018 Jul 10;10(7):230. doi: 10.3390/cancers10070230.
Age is one of the biggest risk factors for ovarian cancer. Older women have higher rates of diagnosis and death associated with the disease. In mouse models, it was shown that aged mice had greater tumor burden than their younger counterparts when intraperitoneally injected with ovarian tumor cells. While very few papers have been published looking at the direct link between ovarian cancer metastasis and age, there is a wealth of information on how age affects metastatic microenvironments. Mesothelial cells, the peritoneal extracellular matrix (ECM), fibroblasts, adipocytes and immune cells all exhibit distinct changes with age. The aged peritoneum hosts a higher number of senescent cells than its younger counterpart, in both the mesothelium and the stroma. These senescent cells promote an inflammatory profile and overexpress Matrix Metalloproteinases (MMPs), which remodel the ECM. The aged ECM is also modified by dysregulated collagen and laminin synthesis, increases in age-related crosslinking and increasing ovarian cancer invasion into the matrix. These changes contribute to a vastly different microenvironment in young and aged models for circulating ovarian cancer cells, creating a more welcoming “soil”.
年龄是卵巢癌最大的风险因素之一。老年女性与该疾病相关的诊断率和死亡率更高。在小鼠模型中，研究表明，当腹腔注射卵巢肿瘤细胞时，老年小鼠比年轻小鼠的肿瘤负担更重。虽然很少有论文探讨卵巢癌转移与年龄之间的直接联系，但关于年龄如何影响转移微环境有大量信息。间皮细胞、腹膜细胞外基质（ECM）、成纤维细胞、脂肪细胞和免疫细胞都会随着年龄增长呈现出明显变化。在间皮和基质中，老年腹膜中的衰老细胞数量均高于年轻腹膜。这些衰老细胞促进炎症反应并过度表达基质金属蛋白酶（MMPs），从而重塑细胞外基质。衰老的细胞外基质还会因胶原蛋白和层粘连蛋白合成失调、与年龄相关的交联增加以及卵巢癌向基质的浸润增加而发生改变。这些变化导致年轻和老年模型中循环卵巢癌细胞所处的微环境截然不同，从而营造出更适宜的“土壤”。
