A multiscale study revealing the interplay between tumor growth and the three-dimensional extracellular matrix
Authors
Gong, Xiangyu
ORCID
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Other Contributors
Mills, Kristen L.
Oberai, Assad
Liu, Li (Emily)
Ligon, Lee
Oberai, Assad
Liu, Li (Emily)
Ligon, Lee
Issue Date
2019-12
Keywords
Mechanical engineering
Degree
PhD
Terms of Use
Attribution-NonCommercial-NoDerivs 3.0 United States
This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
This electronic version is a licensed copy owned by Rensselaer Polytechnic Institute, Troy, NY. Copyright of original work retained by author.
Full Citation
Abstract
To study biological processes of cancer progression is not an easy task – effort has been made to develop novel in vitro platforms that recapitulate physical features of the tumor microenvironment (TME) for cancer research. This dissertation covers three main topics attempting to further the effort on in vitro tumor models: (I) biomechanics of tumor growth in a three-dimensional (3D) mechanical context and local mechanical stress correlated to tumor shape; (II) the role of collagen structure in cancer progression; and (III) the intrinsic heterogeneity with which a population of cancer cells interacts with 3D matrices. Using interdisciplinary approaches, this work aims to evaluate mechanical principles and tissue architecture that regulate tumor growth and progression, and to better understand cancer heterogeneous response to 3D in vitro models. Our results may provide insights on how physical cues affect cancer cell behavior and tumor growth, and raise the awareness of the importance of cancer heterogeneity in cancer research.
In healthy tissues, biomechanical signals, such as tissue stiffness and mechanical stress, provide important governing signals that direct cell division, motility, and differentiation. Increased tissue stiffness and mechanical stress are, in general, associated with solid tumor growth; therefore, it is not surprising that biomechanical signaling becomes deregulated. Furthermore, the increased tissue stiffness is often related to overexpression and excessive crosslinking of extracellular matrix (ECM) components, such as collagen, during tumor progression. Therefore, the extracellular matrix surrounding the tumor will be reorganized and densified, which favors tumor cell invasion, the first step in metastasis. Whereas a biomechanical understanding of healthy tissue processes is being gained from governing geometric (cell shape) and biophysical (mechanical tension) cues, and their integration with the responsible molecular mechanisms is being elucidated, the same cannot be said of tumor development, which is characterized by aberrant growth patterns.
In healthy tissues, biomechanical signals, such as tissue stiffness and mechanical stress, provide important governing signals that direct cell division, motility, and differentiation. Increased tissue stiffness and mechanical stress are, in general, associated with solid tumor growth; therefore, it is not surprising that biomechanical signaling becomes deregulated. Furthermore, the increased tissue stiffness is often related to overexpression and excessive crosslinking of extracellular matrix (ECM) components, such as collagen, during tumor progression. Therefore, the extracellular matrix surrounding the tumor will be reorganized and densified, which favors tumor cell invasion, the first step in metastasis. Whereas a biomechanical understanding of healthy tissue processes is being gained from governing geometric (cell shape) and biophysical (mechanical tension) cues, and their integration with the responsible molecular mechanisms is being elucidated, the same cannot be said of tumor development, which is characterized by aberrant growth patterns.
Description
December 2019
School of Engineering
School of Engineering
Department
Dept. of Mechanical, Aerospace, and Nuclear Engineering
Publisher
Rensselaer Polytechnic Institute, Troy, NY
Relationships
Rensselaer Theses and Dissertations Online Collection
Access
CC BY-NC-ND. Users may download and share copies with attribution in accordance with a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. No commercial use or derivatives are permitted without the explicit approval of the author.