Brain and Breast Cancer Cells with PTEN Loss of Function Reveal Enhanced Durotaxis and RHOB Dependent Amoeboid Migration Utilizing 3D Scaffolds and Aligned Microfiber Tracts
Author
Wieland, AnnalenaStrissel, Pamela L
Schorle, Hannah
Bakirci, Ezgi
Janzen, Dieter
Beckmann, Matthias W
Eckstein, Markus
Dalton, Paul D
Strick, Reiner
Date
2021-10-14Journal
CancersPublisher
MDPI AGType
Article
Metadata
Show full item recordAbstract
Background: Glioblastoma multiforme (GBM) and metastatic triple-negative breast cancer (TNBC) with PTEN mutations often lead to brain dissemination with poor patient outcome, thus new therapeutic targets are needed. To understand signaling, controlling the dynamics and mechanics of brain tumor cell migration, we implemented GBM and TNBC cell lines and designed 3D aligned microfibers and scaffolds mimicking brain structures. Methods: 3D microfibers and scaffolds were printed using melt electrowriting. GBM and TNBC cell lines with opposing PTEN genotypes were analyzed with RHO-ROCK-PTEN inhibitors and PTEN rescue using live-cell imaging. RNA-sequencing and qPCR of tumor cells in 3D with microfibers were performed, while scanning electron microscopy and confocal microscopy addressed cell morphology. Results: In contrast to the PTEN wildtype, GBM and TNBC cells with PTEN loss of function yielded enhanced durotaxis, topotaxis, adhesion, amoeboid migration on 3D microfibers and significant high RHOB expression. Functional studies concerning RHOB-ROCK-PTEN signaling confirmed the essential role for the above cellular processes. Conclusions: This study demonstrates a significant role of the PTEN genotype and RHOB expression for durotaxis, adhesion and migration dependent on 3D. GBM and TNBC cells with PTEN loss of function have an affinity for stiff brain structures promoting metastasis. 3D microfibers represent an important tool to model brain metastasizing tumor cells, where RHO-inhibitors could play an essential role for improved therapy.Keyword
3D microfiber3D tumor model
PTEN
RHO
ROCK
amoeboid cell migration
brain cancer
breast cancer
durotaxis
topotaxis
Identifier to cite or link to this item
http://hdl.handle.net/10713/16949ae974a485f413a2113503eed53cd6c53
10.3390/cancers13205144
Scopus Count
Collections
Related articles
- KIF13A-regulated RhoB plasma membrane localization governs membrane blebbing and blebby amoeboid cell migration.
- Authors: Gong X, Didan Y, Lock JG, Strömblad S
- Issue date: 2018 Sep 3
- Cell surface area and membrane folding in glioblastoma cell lines differing in PTEN and p53 status.
- Authors: Memmel S, Sukhorukov VL, Höring M, Westerling K, Fiedler V, Katzer A, Krohne G, Flentje M, Djuzenova CS
- Issue date: 2014
- Engineered Three-Dimensional Scaffolds Modulating Fate of Breast Cancer Cells Using Stiffness and Morphology Related Cell Adhesion.
- Authors: Hanumantharao SN, Que CA, Vogl BJ, Rao S
- Issue date: 2020
- Dual Targeting of Mesenchymal and Amoeboid Motility Hinders Metastatic Behavior.
- Authors: Jones BC, Kelley LC, Loskutov YV, Marinak KM, Kozyreva VK, Smolkin MB, Pugacheva EN
- Issue date: 2017 Jun
- Phytochemicals inhibit migration of triple negative breast cancer cells by targeting kinase signaling.
- Authors: Shahi Thakuri P, Gupta M, Singh S, Joshi R, Glasgow E, Lekan A, Agarwal S, Luker GD, Tavana H
- Issue date: 2020 Jan 2