失巢
浆液性癌
癌症研究
内分泌学
内科学
医学
去甲肾上腺素
肿瘤微环境
下调和上调
浆液性液体
癌症
卵巢癌
生物
癌细胞
多巴胺
生物化学
基因
作者
Hunter D. Reavis,Stefan Gysler,Grace B. McKenney,Matthew Knarr,Hannah Lusk,Priyanka Rawat,Hannah S. Rendulich,Matthew D. Mitchell,Dara S. Berger,Ju Hyun Moon,Suyeon Ryu,Monica Mainigi,Marcin P. Iwanicki,Dave S.B. Hoon,Laura M. Sanchez,Ronny Drapkin
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2024-01-25
标识
DOI:10.1172/jci.insight.170961
摘要
High grade serous carcinoma (HGSC) is the most lethal gynecological malignancy in the United States. Late diagnosis and the emergence of chemoresistance have prompted studies into how the tumor microenvironment, and more recently tumor innervation, may be leveraged for HGSC prevention and interception. In addition to biobehavioral sources, concentrations of the sympathetic neurotransmitter norepinephrine (NE) in the ovary increase during ovulation and after menopause. Importantly, NE exacerbates advanced HGSC progression. However, little is known about the role of NE in early disease pathogenesis. Here, we investigated the role of NE in instigating anchorage independence and micrometastasis of preneoplastic lesions from the fallopian tube epithelium (FTE) to the ovary, an essential step in HGSC onset. We found that in the presence of NE, FTE cell lines are able to survive in ultra-low attachment (ULA) culture in a beta-adrenergic receptor (β-AR)-dependent manner. Importantly, spheroid formation and cell viability conferred by treatment with physiological sources of NE can be abrogated using the beta-adrenergic receptor blocker propranolol. We have also identified that NE-mediated anoikis resistance may be attributable to downregulation of colony stimulating factor 2 (CSF2). These findings provide mechanistic insight and identify targets that may be regulated by ovarian-derived NE in early HGSC.
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