Inflammation is a key contributor to ovarian cancer cell seeding.
Inflammation is a key contributor to ovarian cancer cell seeding.
复制标题
DOI：
10.1038/s41598-018-30261-8
复制
发表时间：
2018-08-17
影响因子：
4.6
通讯作者：
Orsulic S
中科院分区：
文献类型：
--
作者：
Jia D;Nagaoka Y;Katsumata M;Orsulic S
卵巢癌的发病率在绝经早期显著增加，但导致癌症发生的因素尚不清楚。大多数卵巢癌起源于输卵管，随后将恶性细胞植入卵巢。然而，导致癌细胞植入的事件和条件尚不清楚。为了量化哪些条件有利于在免疫活性小鼠模型中种植癌细胞，我们通过外科手术将小鼠卵巢癌细胞移植到同基因小鼠的输卵管中，并模拟与排卵伤口修复、持续排卵、卵巢表面疤痕形成和衰老相关的条件。我们发现癌细胞种植的主要部位不是卵巢，而是附近的手术伤口部位，这与强烈和持续的炎症反应有关。卵巢中与炎症相关的情况，如急性排卵伤口修复，卵巢表面疤痕的活跃愈合，以及小鼠的衰老，导致癌细胞在手术伤口部位和卵巢周围组织中种植增加。卵巢中不伴有炎症的变化，如完整的排卵周期和卵巢表面完全愈合的疤痕，并不会增加癌细胞的种植。我们得出结论，炎症是排卵和绝经后事件导致卵巢癌风险增加的最可能的机制。
The incidence of ovarian cancer dramatically increases in early menopause but the factors contributing to cancer onset are unclear. Most ovarian cancers originate in the fallopian tube with subsequent implantation of malignant cells into the ovary. However, the events and conditions that lead to cancer cell implantation are unknown. To quantify which conditions are conducive to the seeding of cancer cells in an immunocompetent mouse model, we surgically implanted mouse ovarian cancer cells into the oviducts of syngeneic mice and simulated conditions associated with ovulatory wound repair, incessant ovulation, ovarian surface scarring, and aging. We found that the dominant site of cancer cell seeding was not the ovary but the nearby surgical wound site, which was associated with a strong and persistent inflammatory reaction. Conditions in the ovary associated with inflammation, such as acute ovulatory wound repair, active healing of the scarred ovarian surface, and mouse aging, contributed to increased seeding of the cancer cells to the surgical wound site and tissues surrounding the ovary. Changes in the ovary not accompanied by inflammation, such as completed ovulatory cycles and fully-healed scars on the ovarian surface, did not contribute to increased cancer cell seeding. We conclude that inflammation is the most likely mechanism by which ovulation and postmenopausal events contribute to the increased risk of ovarian cancer.
登录
查看更多内容
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
6.4
作者：
Purdie, DM;Bain, CJ;Green, AC
通讯作者：
Green, AC
影响因子：
5.6
作者：
Kindelberger, David W.;Lee, Yonghee;Crum, Christopher P.
通讯作者：
Crum, Christopher P.
影响因子：
13.8
作者：
Morihara, Kiyoshi;Takenaka, Hideya;Kishimoto, Saburo
通讯作者：
Kishimoto, Saburo
DOI：
10.1016/j.bbrc.2015.05.083
发表时间：
2015-08-07
影响因子：
3.1
作者：
Huang, Jing;Wang, Lei;Goldberg, Michael S.
通讯作者：
Goldberg, Michael S.