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Updated: Mar 20, 2026
Modeling Ovarian Cancer Multicellular Spheroid Behavior in a Dynamic 3D Peritoneal Microdevice
Published on: February 18, 2017
Stemness and chemoresistance in epithelial ovarian carcinoma cells under shear stress
Carman K M Ip1, Shan-Shan Li1, Matthew Y H Tang2
1School of Biological Sciences, University of Hong Kong, Pokfulam Road, Hong Kong.
Abstract:
One of greatest challenges to the successful treatment of cancer is drug resistance. An exciting approach is the eradication of cancer stem cells (CSCs). However, little is known about key signals regulating the formation and expansion of CSCs. Moreover, lack of a reliable predictive preclinical model has been a major obstacle to discover new cancer drugs and predict their clinical activity. Here, in ovarian cancer, a highly chemoresistant tumor that is rapidly fatal, we provide the first evidence demonstrating the causal involvement of mechanical stimulus in the CSC phenotype using a customizable microfluidic platform and three-dimensional spheroids, which most closely mimic tumor behavior. We found that ovarian cancer cells significantly acquired the expression of epithelial-to-mesenchymal transition and CSC markers and a remarkable chemoresistance to clinically relevant doses of frontline chemotherapeutic drugs cisplatin and paclitaxel when grown under fluid shear stress, which corroborates with the physiological attainable levels in the malignant ascites, but not under static condition. Furthermore, we uncovered a new link of microRNA-199a-3p, phosphatidylinositol 3-kinase/Akt, and multidrug transporter activation in shear stress-induced CSC enrichment. Our findings shed new light on the significance of hydrodynamics in cancer progression, emphasizing the need of a flow-informed framework in the development of therapeutics.
Insights
Mechanical forces, specifically fluid shear stress, promote cancer stem cell (CSC) traits and chemoresistance in ovarian cancer. This highlights the role of hydrodynamics in cancer progression and drug development.
Area of Science:
- Oncology
- Biophysics
- Biomedical Engineering
Background:
- Drug resistance is a major challenge in cancer treatment.
- Cancer stem cells (CSCs) are implicated in tumor recurrence and therapy resistance.
- Ovarian cancer is highly chemoresistant and rapidly fatal, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the role of mechanical stimuli in regulating CSC phenotype in ovarian cancer.
- To establish a predictive preclinical model for ovarian cancer drug discovery.
- To identify key molecular mechanisms underlying shear stress-induced CSC enrichment.
Main Methods:
- Utilized a customizable microfluidic platform and 3D spheroids to mimic tumor microenvironment.
- Exposed ovarian cancer cells to physiological levels of fluid shear stress.
- Assessed expression of epithelial-to-mesenchymal transition (EMT) and CSC markers.
- Evaluated chemoresistance to cisplatin and paclitaxel.
- Investigated the role of microRNA-199a-3p, PI3K/Akt pathway, and multidrug transporters.
Main Results:
- Fluid shear stress significantly induced EMT and CSC markers in ovarian cancer cells.
- Shear stress exposure led to remarkable chemoresistance to cisplatin and paclitaxel.
- Static conditions did not induce these changes.
- Uncovered a novel link between microRNA-199a-3p, PI3K/Akt pathway, and multidrug transporter activation in shear stress-induced CSC enrichment.
Conclusions:
- Mechanical stimulus, specifically fluid shear stress, causally influences the CSC phenotype and chemoresistance in ovarian cancer.
- Hydrodynamics play a significant role in cancer progression.
- A flow-informed framework is crucial for developing effective cancer therapeutics.
