Novel Morphologic and Genetic Analysis of Cancer Cells in a 3D Microenvironment Identifies STAT3 as a Regulator of Tumor Permeability Barrier Function

doi:10.1158/0008-5472.CAN-14-2611

	Novel Morphologic and Genetic Analysis of Cancer Cells in a 3D Microenvironment Identifies STAT3 as a Regulator of Tumor Permeability Barrier Function
	Park, Min Chul 4,5; Jeong, Hyobin 6; Son, Sung Hwa 4; Kim, YounHa 4,7; Han, Daeyoung 4,7; Goughnour, Peter C.4,7; Kang, Taehee 4; Kwon, Nam Hoon 4; Moon, Hyo Eun 8; Paek, Sun Ha 8
刊名	CANCER RESEARCH
	2016-03-01
卷号	76 期号:5 页码:1044-1054
ISSN号	0008-5472
DOI	10.1158/0008-5472.CAN-14-2611
文献子类	Article
英文摘要	Tumor permeability is a critical determinant of drug delivery and sensitivity, but systematic methods to identify factors that perform permeability barrier functions in the tumor microenvironment are not yet available. Multicellular tumor spheroids have become tractable in vitro models to study the impact of a three-dimensional (3D) environment on cellular behavior. In this study, we characterized the spheroid-forming potential of cancer cells and correlated the resulting spheroid morphologies with genetic information to identify conserved cellular processes associated with spheroid structure. Spheroids generated from 100 different cancer cell lines were classified into four distinct groups based on morphology. In particular, round and compact spheroids exhibited highly hypoxic inner cores and permeability barriers against anticancer drugs. Through systematic and correlative analysis, we reveal JAK-STAT signaling as one of the signature pathways activated in round spheroids. Accordingly, STAT3 inhibition in spheroids generated from the established cancer cells and primary glioblastoma patient-derived cells altered the rounded morphology and increased drug sensitivity. Furthermore, combined administration of the STAT3 inhibitor and 5-fluorouracil to a mouse xenograft model markedly reduced tumor growth compared with monotherapy. Collectively, our findings demonstrate the ability to integrate 3D culture and genetic profiling to determine the factors underlying the integrity of the permeability barrier in the tumor microenvironment, and may help to identify and exploit novel mechanisms of drug resistance. (C)2016 AACR.
WOS关键词	SIGNALING INDUCES APOPTOSIS ; DRUG-RESISTANCE ; MULTICELLULAR SPHEROIDS ; MULTIDRUG-RESISTANCE ; COLORECTAL-CANCER ; CULTURE-SYSTEM ; HYPOXIA ; INDUCTION ; BIOLOGY ; ENVIRONMENT
WOS研究方向	Oncology
语种	英语
出版者	AMER ASSOC CANCER RESEARCH
WOS记录号	WOS:000374161800008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276111]
专题	中国科学院上海药物研究所
通讯作者	Kim, Sunghoon
作者单位	1.DGIST, Dept New Biol, Inst Basic Sci, Ctr Syst Biol Plant Senescence & Life Hist, Daegu, South Korea; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 200031, Peoples R China 3.Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurosurg, Seoul, South Korea; 4.Seoul Natl Univ, Med Bioconvergence Res Ctr, Gwanak Ro 599, Seoul 151742, South Korea; 5.Seoul Natl Univ, Adv Inst Convergence Technol, Suwon, South Korea; 6.POSTECH, Sch Interdisciplinary Biosci & Bioengn, Pohang, South Korea; 7.Seoul Natl Univ, Coll Pharm, Grad Sch Convergence Technol, Dept Mol Med & Biopharmaceut Sci, Seoul, South Korea; 8.Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Neurosurg, Seoul, South Korea;
推荐引用方式 GB/T 7714	Park, Min Chul,Jeong, Hyobin,Son, Sung Hwa,et al. Novel Morphologic and Genetic Analysis of Cancer Cells in a 3D Microenvironment Identifies STAT3 as a Regulator of Tumor Permeability Barrier Function[J]. CANCER RESEARCH,2016,76(5):1044-1054.
APA	Park, Min Chul.,Jeong, Hyobin.,Son, Sung Hwa.,Kim, YounHa.,Han, Daeyoung.,...&Kim, Sunghoon.(2016).Novel Morphologic and Genetic Analysis of Cancer Cells in a 3D Microenvironment Identifies STAT3 as a Regulator of Tumor Permeability Barrier Function.CANCER RESEARCH,76(5),1044-1054.
MLA	Park, Min Chul,et al."Novel Morphologic and Genetic Analysis of Cancer Cells in a 3D Microenvironment Identifies STAT3 as a Regulator of Tumor Permeability Barrier Function".CANCER RESEARCH 76.5(2016):1044-1054.