TY  - JOUR
A1  - Wieland, Annalena
A1  - Strissel, Pamela L.
A1  - Schorle, Hannah
A1  - Bakirci, Ezgi
A1  - Janzen, Dieter
A1  - Beckmann, Matthias W.
A1  - Eckstein, Markus
A1  - Dalton, Paul D.
A1  - Strick, Reiner
T1  - 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
JF  - Cancers
N2  - 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.
KW  - 3D tumor model
KW  - 3D microfiber
KW  - amoeboid cell migration
KW  - brain cancer
KW  - breast cancer
KW  - PTEN
KW  - RHO
KW  - ROCK
KW  - durotaxis
KW  - topotaxis
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248443
SN  - 2072-6694
VL  - 13
IS  - 20
ER  - 
TY  - JOUR
A1  - An, Ran
A1  - Strissel, Pamela L.
A1  - Al-Abboodi, Majida
A1  - Robering, Jan W.
A1  - Supachai, Reakasame
A1  - Eckstein, Markus
A1  - Peddi, Ajay
A1  - Hauck, Theresa
A1  - Bäuerle, Tobias
A1  - Boccaccini, Aldo R.
A1  - Youssef, Almoatazbellah
A1  - Sun, Jiaming
A1  - Strick, Reiner
A1  - Horch, Raymund E.
A1  - Boos, Anja M.
A1  - Kengelbach-Weigand, Annika
T1  - An innovative arteriovenous (AV) loop breast cancer model tailored for cancer research
JF  - Bioengineering
N2  - Animal models are important tools to investigate the pathogenesis and develop treatment strategies for breast cancer in humans. In this study, we developed a new three-dimensional in vivo arteriovenous loop model of human breast cancer with the aid of biodegradable materials, including fibrin, alginate, and polycaprolactone. We examined the in vivo effects of various matrices on the growth of breast cancer cells by imaging and immunohistochemistry evaluation. Our findings clearly demonstrate that vascularized breast cancer microtissues could be engineered and recapitulate the in vivo situation and tumor-stromal interaction within an isolated environment in an in vivo organism. Alginate–fibrin hybrid matrices were considered as a highly powerful material for breast tumor engineering based on its stability and biocompatibility. We propose that the novel tumor model may not only serve as an invaluable platform for analyzing and understanding the molecular mechanisms and pattern of oncologic diseases, but also be tailored for individual therapy via transplantation of breast cancer patient-derived tumors.
KW  - arteriovenous loop
KW  - breast cancer
KW  - animal model
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-278919
SN  - 2306-5354
VL  - 9
IS  - 7
ER  -