Hudson Institute of Medical Research, Clayton VIC 3168, Australia.
Department of Molecular and Translational Sciences, Monash University, Clayton VIC 3800, Australia.
Int J Mol Sci. 2019 Mar 22;20(6):1466. doi: 10.3390/ijms20061466.
Ovarian cancer is the seventh most commonly diagnosed cancer amongst women and has the highest mortality rate of all gynaecological malignancies. It is a heterogeneous disease attributed to one of three cell types found within the reproductive milieu: epithelial, stromal, and germ cell. Each histotype differs in etiology, pathogenesis, molecular biology, risk factors, and prognosis. Furthermore, the origin of ovarian cancer remains unclear, with ovarian involvement secondary to the contribution of other gynaecological tissues. Despite these complexities, the disease is often treated as a single entity, resulting in minimal improvement to survival rates since the introduction of platinum-based chemotherapy over 30 years ago. Despite concerted research efforts, ovarian cancer remains one of the most difficult cancers to detect and treat, which is in part due to the unique mode of its dissemination. Ovarian cancers tend to invade locally to neighbouring tissues by direct extension from the primary tumour, and passively to pelvic and distal organs within the peritoneal fluid or ascites as multicellular spheroids. Once at their target tissue, ovarian cancers, like most epithelial cancers including colorectal, melanoma, and breast, tend to invade as a cohesive unit in a process termed collective invasion, driven by specialized cells termed "leader cells". Emerging evidence implicates leader cells as essential drivers of collective invasion and metastasis, identifying collective invasion and leader cells as a viable target for the management of metastatic disease. However, the development of targeted therapies specifically against this process and this subset of cells is lacking. Here, we review our understanding of metastasis, collective invasion, and the role of leader cells in ovarian cancer. We will discuss emerging research into the development of novel therapies targeting collective invasion and the leader cell population.
卵巢癌是女性中第七种最常见的癌症，也是所有妇科恶性肿瘤中死亡率最高的。它是一种异质性疾病，归因于生殖环境中发现的三种细胞类型之一：上皮、基质和生殖细胞。每种组织类型在病因、发病机制、分子生物学、危险因素和预后方面都有所不同。此外，卵巢癌的起源仍不清楚，卵巢受累是其他妇科组织贡献的结果。尽管存在这些复杂性，但该疾病通常被视为单一实体，自 30 多年前引入铂类化疗以来，生存率几乎没有改善。尽管进行了协同研究努力，但卵巢癌仍然是最难检测和治疗的癌症之一，部分原因是其独特的传播方式。卵巢癌往往通过原发肿瘤的直接扩展向邻近组织局部侵袭，并作为多细胞球体在腹膜液或腹水内向骨盆和远处器官被动扩散。一旦到达目标组织，卵巢癌就像包括结直肠癌、黑色素瘤和乳腺癌在内的大多数上皮癌一样，倾向于以一种称为集体侵袭的过程中作为一个有凝聚力的单位侵袭，这一过程由称为“先导细胞”的特殊细胞驱动。新出现的证据表明，先导细胞是集体侵袭和转移的重要驱动因素，将集体侵袭和先导细胞确定为管理转移性疾病的可行靶点。然而，针对这一过程和这一小部分细胞开发靶向治疗的方法仍然缺乏。在这里，我们回顾了我们对转移、集体侵袭以及先导细胞在卵巢癌中的作用的理解。我们将讨论针对集体侵袭和先导细胞群体开发新型治疗方法的新兴研究。
