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  - 
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  - Schmid, Rafael
A1  - Schmidt, Sonja K.
A1  - Hazur, Jonas
A1  - Detsch, Rainer
A1  - Maurer, Evelyn
A1  - Boccaccini, Aldo R.
A1  - Hauptstein, Julia
A1  - Teßmar, Jörg
A1  - Blunk, Torsten
A1  - Schrüfer, Stefan
A1  - Schubert, Dirk W.
A1  - Horch, Raymund E.
A1  - Bosserhoff, Anja K.
A1  - Arkudas, Andreas
A1  - Kengelbach-Weigand, Annika
T1  - Comparison of hydrogels for the development of well-defined 3D cancer models of breast cancer and melanoma
JF  - Cancers
N2  - Bioprinting offers the opportunity to fabricate precise 3D tumor models to study tumor pathophysiology and progression. However, the choice of the bioink used is important. In this study, cell behavior was studied in three mechanically and biologically different hydrogels (alginate, alginate dialdehyde crosslinked with gelatin (ADA–GEL), and thiol-modified hyaluronan (HA-SH crosslinked with PEGDA)) with cells from breast cancer (MDA-MB-231 and MCF-7) and melanoma (Mel Im and MV3), by analyzing survival, growth, and the amount of metabolically active, living cells via WST-8 labeling. Material characteristics were analyzed by dynamic mechanical analysis. Cell lines revealed significantly increased cell numbers in low-percentage alginate and HA-SH from day 1 to 14, while only Mel Im also revealed an increase in ADA–GEL. MCF-7 showed a preference for 1% alginate. Melanoma cells tended to proliferate better in ADA–GEL and HA-SH than mammary carcinoma cells. In 1% alginate, breast cancer cells showed equally good proliferation compared to melanoma cell lines. A smaller area was colonized in high-percentage alginate-based hydrogels. Moreover, 3% alginate was the stiffest material, and 2.5% ADA–GEL was the softest material. The other hydrogels were in the same range in between. Therefore, cellular responses were not only stiffness-dependent. With 1% alginate and HA-SH, we identified matrices that enable proliferation of all tested tumor cell lines while maintaining expected tumor heterogeneity. By adapting hydrogels, differences could be accentuated. This opens up the possibility of understanding and analyzing tumor heterogeneity by biofabrication.
KW  - breast cancer
KW  - melanoma
KW  - biofabrication
KW  - hydrogel
KW  - tumor heterogeneity
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211195
SN  - 2072-6694
VL  - 12
IS  - 8
ER  -