title: Scaffold-Free Coculture Spheroids of Human Colonic Adenocarcinoma Cells and Normal Colonic Fibroblasts Promote Tumorigenicity in Nude Mice.
abstract: The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs) and normal colonic fibroblasts (NCFs) and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D) scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α) by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Jisu
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pathology, Cancer Research Institute, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Ju-Lee
authors.initials: JL
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Hong-Bum
authors.initials: HB
authors.lastname: Park
authors.affiliation: Chungnam National University Hospital Biobank, Daejeon, Republic of Korea.
authors.forename: Su-Yel
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Surgery, Division of Colorectal Surgery, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Jaekye
authors.initials: J
authors.lastname: Sung
authors.affiliation: Department of Pathology, Cancer Research Institute, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Jin Man
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Cancer Research Institute, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
authors.forename: Kyu Sang
authors.initials: KS
authors.lastname: Song
authors.affiliation: Department of Pathology, Cancer Research Institute, Chungnam National University School of Medicine, Daejeon, Republic of Korea. Electronic address: phone330@cnu.ac.kr.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim