Basement membrane invasion during breast cancer
Abstract/Contents
- Abstract
- In epithelial cancers, cells must invade through basement membranes (BMs) to metastasize. The BM, a thin layer of extracellular matrix (ECM) underlying epithelial and endothelial tissues, is primarily composed of laminin and collagen IV and serves as a structural barrier to cancer cell invasion, intravasation, and extravasation. Bm invasion has been thought to require protease degradation since cells, which are typically on the order of 10um in size, are too large to squeeze through the nanometer-scale pores of the BM. However, recent studies point toward a more complex picture, with physical forces generated by cancer cells facilitating protease-independent BM invasion. In this dissertation, I present work studying the impact of ECM mechanics on cancer cell invasion of the BM during breast cancer progression. Specifically, I will present work investigating the impact of ECM stiffness on the ability of cancer cells to form invadopodia protrusions in three-dimensional (3D) BM-like matrices. We show that increased stiffness of BM-like matrices diminishes invadopodia protrusion formation and cancer cell migration, contrasting the results from traditional 2D culture studies. Additionally, I will discuss my work on the development of a 3D in vitro model of collective invasion through endogenously produced BM. We find that cells utilize both proteases and forces to invade through the BM collectively. We also show that cells rely on volume expansion and contractility to exert pulling forces on the BM during invasion. These results reveal new mechanisms underlying breast cancer invasion and may lead to new strategies to inhibiting BM invasion. Ultimately, a comprehensive understanding of the diverse modes of BM invasion may yield new strategies for blocking cancer progression and metastasis.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Chang, Julie |
|---|---|
| Degree supervisor | Chaudhuri, Ovijit |
| Thesis advisor | Chaudhuri, Ovijit |
| Thesis advisor | Dunn, Alexander Robert |
| Thesis advisor | Yang, Fan, (Bioengineering researcher and teacher) |
| Degree committee member | Dunn, Alexander Robert |
| Degree committee member | Yang, Fan, (Bioengineering researcher and teacher) |
| Associated with | Stanford University, Department of Bioengineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Julie Chang. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/rw826bt2444 |
Access conditions
- Copyright
- © 2022 by Julie Chang
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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