title: Encapsulated human hepatocellular carcinoma cells by alginate gel beads as an in vitro metastasis model.
abstract: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and often forms metastases, which are the most important prognostic factors. For further elucidation of the mechanism underlying the progression and metastasis of HCC, a culture system mimicking the in vivo tumor microenvironment is needed. In this study, we investigated the metastatic ability of HCC cells cultured within alginate gel (ALG) beads. In the culture system, HCC cells formed spheroids by proliferation and maintained in nuclear abnormalities. The gene and protein expression of metastasis-related molecules was increased in ALG beads, compared with the traditional adhesion culture. Furthermore, several gene expression levels in ALG bead culture system were even closer to liver cancer tissues. More importantly, in vitro invasion assay showed that the invasion cells derived from ALG beads was 7.8-fold higher than adhesion cells. Our results indicated that the in vitro three-dimensional (3D) model based on ALG beads increased metastatic ability compared with adhesion culture, even partly mimicked the in vivo tumor tissues. Moreover, due to the controllable preparation conditions, steady characteristics and production at large-scale, the 3D ALG bead model would become an important tool used in the high-throughput screening of anti-metastasis drugs and the metastatic mechanism research.
authors.affiliation: Laboratory of Biomedical Material Engineering, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, PR China.
authors.forename: Xiao-xi
authors.initials: XX
authors.lastname: Xu
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Shu-jun
authors.initials: SJ
authors.lastname: Wang
authors.forename: Guang-wei
authors.initials: GW
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Ma
mesh_terms: D000464:Alginates / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008863:Microspheres; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000473:pathology; D014158:Transcription, Genetic; D059016:Tumor Microenvironment
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D020782:Matrix Metalloproteinases
keywords: Alginate bead; Invasion; Matrix metalloproteinase; Metastasis model; Tumor microenvironment