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Fluid shear stress in a logarithmic microfluidic device enhances cancer cell stemness marker expression
Sanat Kumar Dash1,2, Bamadeb Patra2, Vineeta Sharma2
1Department of Mechanical Engineering, Indian Institute of Technology, Madras, Chennai, India.
Lab on a Chip
|May 11, 2022
Summary
Fluid shear stress (FSS) influences cancer cell stemness and drug resistance. This study used a microfluidic device to show how varying FSS levels impact cervical cancer cells, revealing mechanisms relevant to metastasis and relapse.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Mechanobiology
Background:
- Fluid shear stress (FSS) plays a role in cancer cell survival and tumor progression.
- Cancer cells encounter diverse FSS levels within the tumor microenvironment and during metastasis.
- The impact of varying FSS magnitudes on cancer cell stemness and drug resistance remains incompletely understood.
Purpose of the Study:
- To investigate the effects of a wide range of physiological FSS on stemness and drug resistance in HeLa cervical cancer cells.
- To characterize FSS-induced changes in cell proliferation, cell cycle, and cellular stress responses.
- To elucidate the relationship between FSS, stemness marker expression, and drug resistance.
Main Methods:
- Utilized a custom-designed microfluidic device to apply four orders of magnitude of FSS to HeLa cells.
- Performed cell cycle analysis and EdU staining to assess cell proliferation and mitotic arrest.
- Measured intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential.
- Quantified the expression of stemness-related genes (Sox2, N-cadherin) and cell surface markers (CD44, CD33, CD117).
- Assessed doxorubicin drug resistance.
Main Results:
- FSS treatment altered cell proliferation, inducing mitotic arrest, with increased proliferation at medium to low FSS and suppression at high FSS.
- HeLa cells exhibited enhanced tolerance to intracellular ROS and maintained mitochondrial membrane potential under FSS.
- FSS significantly upregulated stemness markers (Sox2, N-cadherin) and cell surface markers (CD44, CD33, CD117) in a magnitude-dependent manner.
- Increased stemness-like properties correlated with enhanced resistance to doxorubicin.
Conclusions:
- FSS mechanotransduction significantly influences cancer cell stemness and drug resistance.
- The microfluidic device provides a platform to study FSS effects on cancer cell behavior relevant to metastasis and relapse.
- Understanding FSS-mediated mechanisms can inform strategies for treating drug-resistant cancers.
