Heterotypic CAF-tumor spheroids promote early peritoneal metastatis of ovarian cancer.

Autor:	Gao Q; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China qingleigao@hotmail.com., Yang Z; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Xu S; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Li X; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Yang X; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Jin P; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Liu Y; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Zhou X; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Zhang T; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Gong C; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Wei X; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Liu D; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Sun C; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Chen G; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Hu J; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Meng L; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Zhou J; Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Sawada K; Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Yamadaoka Suita, Osaka, Japan., Fruscio R; Clinic of Obstetrics and Gynecology, San Gerardo Hospital, Monza, Italy.; Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy., Grunt TW; Signaling Networks Program, Division of Oncology, Department of Medicine I, Comprehensive Cancer Center & Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria., Wischhusen J; Department of Obstetrics and Gynecology, Experimental Tumor Immunology, University of Würzburg Medical School, Würzburg, Germany., Vargas-Hernández VM; Dirección de Investigación, Hospital Juárez de México D.F., Nápoles, Mexico City, Mexico., Pothuri B; Division of Gynecological Oncology, NYU Langone Medical Center, Perlmutter Cancer Center, New York, NY., Coleman RL; Department of Gynecological Oncology & Reproductive Medicine, University of Texas, M.D. Anderson Cancer Center, Houston, TX.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2019 Mar 04; Vol. 216 (3), pp. 688-703. Date of Electronic Publication: 2019 Feb 01.
DOI:	10.1084/jem.20180765
Abstrakt:	High-grade serous ovarian cancer (HGSOC) is hallmarked by early onset of peritoneal dissemination, which distinguishes it from low-grade serous ovarian cancer (LGSOC). Here, we describe the aggressive nature of HGSOC ascitic tumor cells (ATCs) characterized by integrin α5 high (ITGA5 high ) ATCs, which are prone to forming heterotypic spheroids with fibroblasts. We term these aggregates as metastatic units (MUs) in HGSOC for their advantageous metastatic capacity and active involvement in early peritoneal dissemination. Intriguingly, fibroblasts inside MUs support ATC survival and guide their peritoneal invasion before becoming essential components of the tumor stroma in newly formed metastases. Cancer-associated fibroblasts (CAFs) recruit ITGA5 high ATCs to form MUs, which further sustain ATC ITGA5 expression by EGF secretion. Notably, LGSOC is largely devoid of CAFs and the resultant MUs, which might explain its metastatic delay. These findings identify a specialized MU architecture that amplifies the tumor-stroma interaction and promotes transcoelomic metastasis in HGSOC, providing the basis for stromal fibroblast-oriented interventions in hampering OC peritoneal propagation. (© 2019 Gao et al.)
Databáze:	MEDLINE
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