Correlations between spheroidal phenotype and functionality as cancer model암 모델 세포 스페로이드의 형태와 기능 간 상관관계에 관한 연구

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Cellular spheroids have substantial advantages over traditional 2D monolayers as a cancer model due to its structural characteristics and the metabolic gradient similar to in vivo tumor. In the last three decades, a variety of strategies for spheroid formation have been developed. Although the same types of cells from the same origin are utilized, the spheroids made using different methods can have different characteristics. However, it has been challenging to determine which method would generate most proper and functional spheroids for each cell type. Here we hypothesized that there might be correlations between the morphological characteristics and the functionalities of the cellular spheroids. To verify these relationships, we generated the total of six cancer model types with three different cancer cell lines, namely breast cancer cell line, ovarian cancer cell line, and colorectal cancer cell line, using two representative spheroid generation techniques, scaffold-free and scaffold-based methods. We also defined the metrics to characterize the morphological and functional aspects of the spheroids. For each cancer model, parameters for evaluating the functional traits of the spheroid were chosen based on its typical metastatic route. More specifically, breast cancers, which frequently metastasize through hematogenous/lymphatic routes in vivo, were assessed with 3D invasion assay. On the other hand, ovarian cancers, which mostly metastasize through transcoelomic routes, were evaluated with 2D spreading assay. Colorectal cancer models were rated with both 3D and 2D metrics since they are known to take both hematogenous and transcoelomic routes in vivo for metastasis. Based on comparative analyses of the spheroidal phenotypes and functionality, the spheroidal circularity was suggested as the key parameter for the correlations between the formation and metastatic potential. Breast cancer models made with the scaffold-based method showed high circularities and migrated collectively in 3D environments. Collective migration in 3D environments has been proven to be physiologically relevant. In the case of the ovarian cancer model, spheroids made with scaffold-free methods showed high circularities and better capability of spreading in the 2D environment. Finally, the colorectal cancer models made with both the scaffold-free and scaffold-based methods showed similar circularities and also similar invasiveness. Our results suggested a positive correlation between circularity and metastatic potential. Furthermore, we found that spheroids made in a physiologically relevant condition also exhibited higher circularity. These correlations might shine light on the development of more functionally appropriate cancer models that would reflect actual human tumors of different origins.
Advisors
Shin, Hyun Jongresearcher신현정researcher
Description
한국과학기술원 :기계공학과,
Publisher
한국과학기술원
Issue Date
2018
Identifier
325007
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 기계공학과, 2018.2,[iv, 34 p. :]

Keywords

Cellular spheroids▼acancer model▼acancer metastasis▼aspheroid morphology▼ainvasion assay▼aspreading assay; 세포 스페로이드▼a암 모델▼a암 전이▼a스페로이드 형태▼a침습 분석▼a퍼짐 분석

URI
http://hdl.handle.net/10203/265885
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=733714&flag=dissertation
Appears in Collection
ME-Theses_Master(석사논문)
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