Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-cultures
Abstract Background There is increasing appreciation that non-cancer cells within the tumour microenvironment influence cancer progression and anti-cancer drug efficacy. For metastatic prostate cancer (PCa), the bone marrow microenvironment influences metastasis, drug response, and possibly drug res...
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doaj-e8d35d12755849368460a9a63103d2ff2020-11-25T01:07:40ZengBMCBMC Cancer1471-24072018-05-0118111110.1186/s12885-018-4473-8Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-culturesEman Mosaad0Karen Chambers1Kathryn Futrega2Judith Clements3Michael Robert Doran4Stem Cell Therapies Laboratory, Queensland University of Technology (QUT), Translational Research Institute (TRI)Quadram Institute Bioscience, Norwich Research ParkStem Cell Therapies Laboratory, Queensland University of Technology (QUT), Translational Research Institute (TRI)Australian Prostate Cancer Research Centre – Queensland (APCRC-Q), Translational Research Institute (TRI)Stem Cell Therapies Laboratory, Queensland University of Technology (QUT), Translational Research Institute (TRI)Abstract Background There is increasing appreciation that non-cancer cells within the tumour microenvironment influence cancer progression and anti-cancer drug efficacy. For metastatic prostate cancer (PCa), the bone marrow microenvironment influences metastasis, drug response, and possibly drug resistance. Methods Using a novel microwell platform, the Microwell-mesh, we manufactured hundreds of 3D co-culture microtissues formed from PCa cells and bone marrow stromal cells. We used luciferase-expressing C42B PCa cells to enable quantification of the number of PCa cells in complex microtissue co-cultures. This strategy enabled us to quantify specific PCa cell growth and death in response to drug treatment, in different co-culture conditions. In parallel, we used Transwell migration assays to characterize PCa cell migration towards different 2D and 3D stromal cell populations. Results Our results reveal that PCa cell migration varied depending on the relative aggressiveness of the PCa cell lines, the stromal cell composition, and stromal cell 2D or 3D geometry. We found that C42B cell sensitivity to Docetaxel varied depending on culture geometry, and the presence or absence of different stromal cell populations. By contrast, the C42B cell response to Abiraterone Acetate was dependent on geometry, but not on the presence or absence of stromal cells. Conclusion In summary, stromal cell composition and geometry influences PCa cell migration, growth and drug response. The Microwell-mesh and microtissues are powerful tools to study these complex 3D interactions.http://link.springer.com/article/10.1186/s12885-018-4473-8Prostate cancerBone marrow stromal cellsCo-cultureMicrowell-mesh platform3D culture |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eman Mosaad Karen Chambers Kathryn Futrega Judith Clements Michael Robert Doran |
spellingShingle |
Eman Mosaad Karen Chambers Kathryn Futrega Judith Clements Michael Robert Doran Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-cultures BMC Cancer Prostate cancer Bone marrow stromal cells Co-culture Microwell-mesh platform 3D culture |
author_facet |
Eman Mosaad Karen Chambers Kathryn Futrega Judith Clements Michael Robert Doran |
author_sort |
Eman Mosaad |
title |
Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-cultures |
title_short |
Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-cultures |
title_full |
Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-cultures |
title_fullStr |
Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-cultures |
title_full_unstemmed |
Using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2D and 3D co-cultures |
title_sort |
using high throughput microtissue culture to study the difference in prostate cancer cell behavior and drug response in 2d and 3d co-cultures |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2018-05-01 |
description |
Abstract Background There is increasing appreciation that non-cancer cells within the tumour microenvironment influence cancer progression and anti-cancer drug efficacy. For metastatic prostate cancer (PCa), the bone marrow microenvironment influences metastasis, drug response, and possibly drug resistance. Methods Using a novel microwell platform, the Microwell-mesh, we manufactured hundreds of 3D co-culture microtissues formed from PCa cells and bone marrow stromal cells. We used luciferase-expressing C42B PCa cells to enable quantification of the number of PCa cells in complex microtissue co-cultures. This strategy enabled us to quantify specific PCa cell growth and death in response to drug treatment, in different co-culture conditions. In parallel, we used Transwell migration assays to characterize PCa cell migration towards different 2D and 3D stromal cell populations. Results Our results reveal that PCa cell migration varied depending on the relative aggressiveness of the PCa cell lines, the stromal cell composition, and stromal cell 2D or 3D geometry. We found that C42B cell sensitivity to Docetaxel varied depending on culture geometry, and the presence or absence of different stromal cell populations. By contrast, the C42B cell response to Abiraterone Acetate was dependent on geometry, but not on the presence or absence of stromal cells. Conclusion In summary, stromal cell composition and geometry influences PCa cell migration, growth and drug response. The Microwell-mesh and microtissues are powerful tools to study these complex 3D interactions. |
topic |
Prostate cancer Bone marrow stromal cells Co-culture Microwell-mesh platform 3D culture |
url |
http://link.springer.com/article/10.1186/s12885-018-4473-8 |
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