Bladder cancer-on-a-chip for analysis of tumor transition mechanism
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1
Korea Institute of Science and Technology, Center for Biomaterials, Korea
Metastatic bladder cancer shows 6% survival rate within 5 years of diagnosis and usually causes death after 2 years. Purpose of this study is to evaluate the effect of extracellular matrix proteolytic enzyme MMP-9 and cell adhesion molecule CD44, which are involved in invasion and metastasis of cancer, using muscle-invasive bladder cancer cell line (RT4) and superficial human bladder carcinoma cell line (5637) to more effectively prevent migration and metastasis of bladder cancer. 3-D microfluidic device was created using PDMS and matrigel, mixed ECM similar to bladder tissue was injected into the cell culture channel. After gelation, RT4 and 5637 bladder cancer cell lines were cultured and stained to observe metastasis over time using fluorescence microscope and a confocal microscope. Observation after 2 weeks showed increased expression of CD44 and RT4 muscle-invasive bladder cancer cells compared to 5637 superficial carcinoma cell line. Zymography analysis using sup collected from conditioned medium during RT4 and 5637 cell culture process in microfluidic channel showed the significant increase of MMP-9 gelatin degradation. This result was consistent with the result from Real-time PCR and proved that expression of MMP-9 is a key factor of enhanced metastasis of bladder cancer. Human bladder environment mimicking 3D microfluidic chip allowed more effective observation of cellular interactions when compared to static culture in 2D. The result from this study validated CD44 and MMP-9 to be the key biological factors for migration and metastasis of muscle-invasive bladder cancer.
Figure.1 3D microfluidic device mimicking structural environment of bladder cancer
This study was supported by the KIST Project.
Keywords:
Bio-MEMS,
Lab on a chip,
Cell functionality,
biomimetic culture
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
Poster
Topic:
Biomaterials in microdevices and microarrays
Citation:
Lee
E,
Kwon
C,
Han
H,
Park
J,
Kim
Y,
Ok
M,
Seok
H and
Jeon
H
(2016). Bladder cancer-on-a-chip for analysis of tumor transition mechanism.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.00831
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.