The Development of a Biomimetic In Vitro Model with 3D Spheres of Human Colorectal Cancer Cells embedded within Type I Collagen Gel
Date Issued
2014
Date
2014
Author(s)
Lin, Susan Yun Fan
Abstract
To better understand cancer, the gap between in vivo cancer cells and in vitro cancer cells must be narrowed. Such gap could be bridged by an in vitro cancer cell model that is biomimetic to in vivo cancer cells. While most in vitro cancer cell models are in two dimensions (2D), these 2D models are; however, also largely deviated from in vivo cancer cells. In vitro cancer cell models in three dimensions (3D) are proved to better recapitulate in vivo cancer cells. However, there is no study, so far, that specifies the prerequisites of a biomimetic 3D in vitro cancer cell model. Thus, this study aims to define whether a biomimetic 3D in vitro cancer cell model simply requires 3D cancer cell sphere growth or it also demands the 3D cancer cell sphere growth to be contained within a microenvironment. In this study, three in vitro cancer cell models were developed using human colorectal adenocarcinoma cells. A 2D monolayer model was constructed to comprise adherent 2D cancer cell monolayers cultured on tissue culture polystyrene (TCPS). A 3D spheroid model was created to consist suspension of non-adherent 3D cancer cell spheres cultured on ultra-low attachment surface (ULAS). A 3D gel/scaffold-embedding model was established to contain 3D cancer cell spheres cultured within the type I collagen gel (COL I) specially formulated in this study. Phenotypes of in vivo cancer cells including morphology, viability, cancer stem cell population, stemness, epithelial-mesenchymal transition (EMT), angiogenesis, anti-cancer drug resistance, and in vivo tumorigenicity were analyzed and compared among the three in vitro colorectal cancer cell models developed. The cell morphology of in vivo cancer cells was best duplicated by the 3D cancer cell spheres within COL I followed by the suspension of non-adherent 3D cancer cell spheres on ULAS and then the adherent 2D cancer cell monolayers on TCPS. The cell viability, cancer stem cell population, stemness markers expression, EMT markers expression, angiogenesis marker expression, anti-cancer drug resistance, and in vivo tumorigenicity of the 3D cancer cell spheres within COL I were also the highest followed by the suspension of non-adherent 3D cancer cell spheres on ULAS and then the adherent 2D cancer cell monolayers on TCPS. These results indicated that the 3D cancer cell spheres within COL I were the most biomimetic to in vitro cancer cells followed by the suspension of non-adherent 3D cancer cell spheres on ULAS and then by the adherent 2D cancer cell monolayers on TCPS. Therefore, it could be concluded that for the development of a more biomimetic 3D in vitro cancer cell model, not only 3D cancer cell sphere growth is needed but the 3D cancer cell sphere growth within a microenvironment is also necessitated.
Subjects
仿生
二維/三維體外癌細胞模型
三維球型癌細胞
凝膠/支架嵌入
人類結腸直腸癌
第一型膠原蛋白凝膠
癌症幹細胞
幹性
上皮 - 間質轉化
血管新生
抗癌藥性
體內的致瘤性
SDGs
Type
thesis
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