A Circulating Bioreactor Reprograms Cancer Cells Toward a More Mesenchymal Niche

Calamak, Semih
Ermiş Şen, Menekşe
Sun, Han
Islam, Saiful
Sikora, Michael
Nguyen, Michelle
Hasırcı, Vasıf Nejat
Steinmetz, Lars M.
Demirci, Utkan
Cancer is a complex and heterogeneous disease, and cancer cells dynamically interact with the mechanical microenvironment such as hydrostatic pressure, fluid shear, and interstitial flow. These factors play an essential role in cell fate and circulating tumor cell heterogeneity, and can influence the cellular phenotype. In this study, a peristaltic continuous flow reactor is designed and applied to HCT-116 colorectal carcinoma cells to mimic the fluid dynamics of circulation. With this intervention, a CD44/CD24-cell subpopulation emerges, and 100 genes are significantly regulated. The expression of cells at 4 h in the flow reactor is very similar to TGF-ss treatment, which is an inducer of epithelial-mesenchymal transition. ATF3 and SERPINE1 are significantly upregulated in these groups, suggesting that the mesenchymal transition is induced through this signaling pathway. This flow reactor model is satisfactory on its own to reprogram colorectal cancer cells toward a more mesenchymal niche mimicking circulation of the blood.


A comparative study on EpCAM antibody immobilization on gold surfaces and microfluidic channels for the detection of circulating tumor cells
Cetin, Didem; Okan, Meltem; Bat, Erhan; Külah, Haluk (2020-04-01)
Detection of circulating tumor cells (CTCs) from the bloodstream holds great importance to diagnose cancer at early stages. However, CTCs being extremely rare in blood makes them difficult to reach. In this paper, we introduced different surface modification techniques for the enrichment and detection of MCF-7 in microfluidic biosensor applications using gold surface and EpCAM antibody. Mainly, two different mechanisms were employed to immobilize the antibodies; covalent bonding and bioaffinity interaction....
Systems-level analysis reveals multiple modulators of epithelial-mesenchymal transition and identifies DNAJB4 and CD81 as novel metastasis inducers in breast cancer
Kagiali, Zeynep Cansu Üretmen; Sanal, Erdem; Karayel, Özge; Polat, Ayşe Nur; Saatçi, Özge; Ersan, Pelin Gülizar; Trappe, Kathrin; Renard, Bernhard Y.; Önder, Tamer T.; Tunçbağ, Nurcan; Şahin, Özgür; Özlü, Nurhan (American Society for Biochemistry & Molecular Biology (ASBMB), 2019-09)
Epithelial-mesenchymal transition (EMT) is driven by complex signaling events that induce dramatic biochemical and morphological changes whereby epithelial cells are converted into cancer cells. However, the underlying molecular mechanisms remain elusive. Here, we used mass spectrometry based quantitative proteomics approach to systematically analyze the post-translational biochemical changes that drive differentiation of human mammary epithelial (HMLE) cells into mesenchymal. We identified 314 proteins out...
Different Types of Cell Cycle- and Apoptosis-Related Gene Expressions Alter in Corticosteroid-, Vincristine-, and Melphalan-Resistant U-266 Multiple Myeloma Cell Lines
Mutlu, Pelin; Gündüz, Ufuk (2014-09-01)
Objective: Deregulation of the cell cycle and apoptosis mechanisms in normal cells causes many problems, including cancer. In this study, a genome-wide expression analysis of cell cycle- and apoptosis-related genes in corticosteroid-, vincristine-, and melphalan-resistant U-266 multiple myeloma cell lines was conducted.
Capture of circulating tumor cells from blood on modified gold surfaces inside the microfluidic channels
Çetin, Didem; Külah, Haluk; Department of Biomedical Engineering (2019)
Detection of circulating tumor cells (CTCs) from the bloodstream has a critical role in diagnosing and treatment of cancer. However, the number of CTCs in blood compared to other blood cells are extremely rare. In this thesis, various surface modifications strategies for detection of CTCs are studied in order to be used in the microfluidic detection systems. Functionalizing the gold surface with Self Assembled Monolayers (SAMs) used for attaching the EpCAM antibodies, which made possible to immobilize EpCAM...
A high throughput approach for analysis of cell nuclear deformability at single cell level
Ermis, Menekse; Akkaynak, Derya; Chen, Pu; Demirci, Utkan; Hasırcı, Vasıf Nejat (2016-11-14)
Various physiological and pathological processes, such as cell differentiation, migration, attachment, and metastasis are highly dependent on nuclear elasticity. Nuclear morphology directly reflects the elasticity of the nucleus. We propose that quantification of changes in nuclear morphology on surfaces with defined topography will enable us to assess nuclear elasticity and deformability. Here, we used soft lithography techniques to produce 3 dimensional (3-D) cell culture substrates decorated with micron ...
Citation Formats
S. Calamak et al., “A Circulating Bioreactor Reprograms Cancer Cells Toward a More Mesenchymal Niche,” ADVANCED BIOSYSTEMS, pp. 0–0, 2020, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30376.