Background

Ovarian cancer is the most lethal gynecologic cancer and the fifth leading cause of cancer-related mortality in women worldwide. Despite various attempts to improve the diagnosis and therapy of ovarian cancer patients, the survival rate for these patients is still dismal, mainly because most of them are diagnosed at a late stage. Up to 90% of ovarian cancers arise from neoplastic transformation of ovarian surface epithelial cells, and are usually referred to as epithelial ovarian cancer (EOC). Unlike most human cancers, which are disseminated through blood-borne metastatic routes, EOC has traditionally been thought to be disseminated through direct migration of ovarian tumor cells to the peritoneal cavity and omentum via peritoneal fluid. It has recently been shown, however, that EOC can also be disseminated through blood-borne metastatic routes, challenging previous thoughts about ovarian cancer metastasis.

Conclusions

Here, we review our current understanding of the most updated cellular and molecular mechanisms underlying EOC metastasis and discuss in more detail two main metastatic routes of EOC, i.e., transcoelomic metastasis and hematogenous metastasis. The emerging concept of blood-borne EOC metastasis has led to exploration of the significance of circulating tumor cells (CTCs) as novel and non-invasive prognostic markers in this daunting cancer. We also evaluate the role of tumor stroma, including cancer associated fibroblasts (CAFs), tumor associated macrophages (TAMs), endothelial cells, adipocytes, dendritic cells and extracellular matrix (ECM) components in EOC growth and metastasis. Lastly, we discuss therapeutic approaches for targeting EOC. Unraveling the mechanisms underlying EOC metastasis will open up avenues to the design of new therapeutic options. For instance, understanding the molecular mechanisms involved in the hematogenous metastasis of EOC, the biology of CTCs, and the detailed mechanisms through which EOC cells take advantage of stromal cells may help to find new opportunities for targeting EOC metastasis.

中文翻译：

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目前对上皮性卵巢癌转移的见解-希望和障碍。

背景

卵巢癌是最致命的妇科癌症，也是全世界女性与癌症相关的死亡率的第五大诱因。尽管进行了各种尝试来改善卵巢癌患者的诊断和治疗，但是这些患者的存活率仍然令人沮丧，主要是因为其中大多数是在晚期被诊断出的。多达90％的卵巢癌来自卵巢表面上皮细胞的肿瘤转化，通常被称为上皮性卵巢癌（EOC）。与大多数人类癌症通过血液传播的转移途径扩散不同，传统上认为EOC是通过卵巢肿瘤细胞通过腹膜液直接迁移到腹膜腔和网膜而扩散的。但是，最近发现，EOC也可以通过血液传播的转移途径进行传播，

结论

在这里，我们回顾我们目前对EOC转移的最新细胞和分子机制的了解，并更详细地讨论EOC的两种主要转移途径，即跨腔转移和血源性转移。血源性EOC转移的新兴概念已导致探索循环肿瘤细胞（CTC）作为这种令人生畏的癌症中新的和非侵入性预后标志物的重要性。我们还评估了肿瘤基质（包括癌相关的成纤维细胞（CAF），肿瘤相关的巨噬细胞（TAM），内皮细胞，脂肪细胞，树突状细胞和细胞外基质（ECM）成分）在EOC生长和转移中的作用。最后，我们讨论了针对EOC的治疗方法。揭示EOC转移的潜在机制将为设计新的治疗选择开辟途径。例如，了解EOC血源性转移所涉及的分子机制，CTC的生物学以及EOC细胞利用基质细胞的详细机制可能有助于寻找靶向EOC转移的新机会。