Heterotypic CAF-tumor spheroids promote early peritoneal metastasis of ovarian cancer

• DOI: 10.1084/jem.20180765
• Publication Date: 2019-02-01T20:06:26Z
• Authors: Qinglei Gao; Zongyuan Yang; Sen Xu; Xiaoting Li; Xin Yang; Ping Jin; Yi Liu; Xiaoshui Zhou; Taoran Zhang; Cheng Gong; Xiao Wei; Dan Liu; Chaoyang Sun; Gang Chen; Junbo Hu; Li Meng; Jianfeng Zhou; Kenjiro Sawada; Robert Fruscio; Thomas W. Grunt; Jörg Wischhusen; Víctor Manuel Var...; Bhavana Pothuri; Robert L. Coleman
• Keywords: Cancer-Associated Fibroblasts

High-grade serous ovarian cancer (HGSOC) is hallmarked by early onset of peritoneal dissemination, which distinguishes it from low-grade (LGSOC). Here, we describe the aggressive nature HGSOC ascitic tumor cells (ATCs) characterized integrin α5high (ITGA5high) ATCs, are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in for their advantageous capacity and active involvement dissemination. Intriguingly, fibroblasts inside MUs support ATC survival guide invasion before becoming essential components stroma newly formed metastases. Cancer-associated (CAFs) recruit ITGA5high ATCs form MUs, further sustain ITGA5 expression EGF secretion. Notably, LGSOC largely devoid CAFs resultant might explain its delay. These findings identify a specialized MU architecture that amplifies tumor–stroma interaction promotes transcoelomic metastasis HGSOC, providing basis stromal fibroblast-oriented interventions hampering OC propagation.