Fluid shear stress in a logarithmic microfluidic device enhances cancer cell stemness marker expression
- PMID: 35544034
- DOI: 10.1039/d1lc01139a
Fluid shear stress in a logarithmic microfluidic device enhances cancer cell stemness marker expression
Abstract
Fluid shear stress (FSS) is crucial in cancer cell survival and tumor development. Noteworthily, cancer cells are exposed to several degrees of FSS in the tumor microenvironment and during metastasis. Consequently, the stemness marker expression in cancer cells changes with the FSS signal, although it is unclear how it varies with different magnitudes and during metastasis. The current work explores the stemness and drug resistance characteristics of the cervical cancer cell line HeLa in a microfluidic device with a wide range of physiological FSS. Hence, the microfluidic device was designed to achieve a logarithmic flow distribution in four culture chambers, realizing four orders of biological shear stress on a single chip. The cell cycle analysis demonstrated altered cell proliferation and mitotic arrest after FSS treatment. In addition, EdU staining revealed increased cell proliferation with medium to low FSS, whereas high shear had a suppressing effect. FSS increased competence to withstand higher intracellular ROS and mitochondrial membrane potential in HeLa. Furthermore, stemness-related gene (Sox2, N-cadherin) and cell surface marker (CD44, CD33, CD117) expressions were enhanced by FSS mechanotransduction in a magnitude-dependent manner. In summary, these stemness-like properties were concurrent with the drug resistance capability of HeLa towards doxorubicin. Overall, our microfluidic device elucidates cancer cell survival and drug resistance mechanisms during metastasis and in cancer relapse patients.
Similar articles
-
Long range microfluidic shear device for cellular mechanotransduction studies.Annu Int Conf IEEE Eng Med Biol Soc. 2015;2015:3209-12. doi: 10.1109/EMBC.2015.7319075. Annu Int Conf IEEE Eng Med Biol Soc. 2015. PMID: 26736975
-
Online Analysis of Drug Toxicity to Cells with Shear Stress on an Integrated Microfluidic Chip.ACS Sens. 2019 Feb 22;4(2):521-527. doi: 10.1021/acssensors.8b01696. Epub 2019 Feb 12. ACS Sens. 2019. PMID: 30688066
-
Fluid shear stress induces epithelial-mesenchymal transition (EMT) in Hep-2 cells.Oncotarget. 2016 May 31;7(22):32876-92. doi: 10.18632/oncotarget.8765. Oncotarget. 2016. PMID: 27096955 Free PMC article.
-
Rheological influence upon the glomerular podocyte and resultant mechanotransduction.Kidney Blood Press Res. 2015;40(2):176-87. doi: 10.1159/000368493. Epub 2015 Mar 30. Kidney Blood Press Res. 2015. PMID: 25871438 Review.
-
Biomechanics of vascular mechanosensation and remodeling.Mol Biol Cell. 2016 Jan 1;27(1):7-11. doi: 10.1091/mbc.E14-11-1522. Mol Biol Cell. 2016. PMID: 26715421 Free PMC article. Review.
Cited by
-
A modular microfluidic platform to study how fluid shear stress alters estrogen receptor phenotype in ER+ breast cancer cells.Res Sq [Preprint]. 2023 Oct 10:rs.3.rs-3399118. doi: 10.21203/rs.3.rs-3399118/v1. Res Sq. 2023. Update in: Microsyst Nanoeng. 2024 Feb 16;10:25. doi: 10.1038/s41378-024-00653-0. PMID: 37886527 Free PMC article. Updated. Preprint.
-
Advances in cancer mechanobiology: Metastasis, mechanics, and materials.APL Bioeng. 2024 Mar 5;8(1):011502. doi: 10.1063/5.0186042. eCollection 2024 Mar. APL Bioeng. 2024. PMID: 38449522 Free PMC article. Review.
-
[Hepatocellular Carcinoma-Derived Exosomes: Key Players in Intercellular Communication Within the Tumor Microenvironment].Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Jan 20;55(1):6-12. doi: 10.12182/20240160203. Sichuan Da Xue Xue Bao Yi Xue Ban. 2024. PMID: 38322525 Free PMC article. Chinese.
-
Epithelial and mesenchymal phenotypes determine the dynamics of circulating breast tumor cells in microfluidic capillaries under chemotherapy-induced stress.Biomicrofluidics. 2024 Apr 5;18(2):024106. doi: 10.1063/5.0188861. eCollection 2024 Mar. Biomicrofluidics. 2024. PMID: 38585003 Free PMC article.
-
Deformation under flow and morphological recovery of cancer cells.Lab Chip. 2024 Aug 6;24(16):3930-3944. doi: 10.1039/d4lc00246f. Lab Chip. 2024. PMID: 38993177 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous