卵巢癌
转移
癌症研究
细胞外基质
间质细胞
癌症
生物
肿瘤微环境
卵巢肿瘤
癌细胞
医学
内科学
细胞生物学
作者
Jennifer A. Waters,Mikella Robinson,Omar Lujano-Olazaba,Cassidy C. Lucht,Sarah L. Gilbert,Carrie D. House
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2024-04-18
标识
DOI:10.1158/0008-5472.can-23-2613
摘要
Abstract Ovarian cancer can metastasize to the omentum, which is associated with a complex tumor microenvironment. Omental stromal cells facilitate ovarian cancer colonization by secreting cytokines and growth factors. Improved understanding of the tumor supportive functions of specific cell populations in the omentum could identify strategies to prevent and treat ovarian cancer metastasis. Here, we showed that omental preadipocytes enhance the tumor initiation capacity of ovarian cancer cells. Secreted factors from preadipocytes supported cancer cell viability during nutrient and isolation stress and enabled prolonged proliferation. Co-culturing with pre-adipocytes led to upregulation of genes involved in extracellular matrix (ECM) organization, cellular response to stress, and regulation of insulin-like growth factor (IGF) signaling in ovarian cancer cells. IGF-1 induced ECM genes and increased alternative NF-κB signaling by activating RelB. Inhibiting the IGF-1 receptor (IGF1R) initially increased tumor omental adhesion but decreased growth of established preadipocyte-induced subcutaneous tumors as well as established intraperitoneal tumors. Together, this study shows that omental preadipocytes support ovarian cancer progression, which has implications for targeting metastasis.
科研通智能强力驱动
Strongly Powered by AbleSci AI