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Updated: Oct 7, 2025
Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
Published on: April 2, 2020
Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability
Qiang Liu1,2, Hongliang Shen1,3, Andrew Naguib1
1Department of Urology, Yale University School of Medicine, New Haven, CT, USA.
Abstract:
Prostate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembrane proteins that regulate paracellular permeability and cell polarity, and their levels are elevated in many human cancers such as breast, ovarian, pancreatic, and prostatic cancers. Previously, we found that Cldn3 and Cldn4 are expressed in aggressive high-grade human prostate cancer specimens. We and others have shown that there are higher levels of Cldn3 and Cldn4 in metastatic human prostate cancer cells than in normal human prostate cells. The result of targeting Cldn3 and Cldn4 expression on the growth and viability of prostate cancer cells has not been elucidated. Human prostate cancer PC3 and LNCaP cells were transfected with Cldn3 or -4 small interfering RNAs (siRNAs). Cldn3/Cldn4 siRNA treatment resulted in a greater than 85% decrease in the protein levels of Cldn3 and Cldn4, which was accompanied by a 30-40% decrease in prostate cancer cell growth and a 60-65% reduction in cell viability. There was decreased cell migration with Cldn3 and Cldn4 siRNA in both PC3 and LNCaP cells and a 60-75% decrease in the number of clones when treated with siCldn3 or siCldn4 compared to control. Knocking down Cldn3/Cldn4 affects prostate cancer cell growth and survival and may have therapeutic implications.
Insights
Targeting Claudins 3 and 4 (Cldn3/Cldn4) in prostate cancer cells significantly reduced their growth, viability, and migration. This suggests Cldn3/Cldn4 as potential therapeutic targets for advanced prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Prostate cancer is a prevalent invasive malignancy in the US.
- Claudins (Cldns), transmembrane proteins, are implicated in cancer progression and are elevated in various cancers, including prostate cancer.
- Elevated Cldn3 and Cldn4 levels are observed in aggressive and metastatic prostate cancer specimens.
Purpose of the Study:
- To investigate the functional role of Claudins 3 and 4 (Cldn3/Cldn4) in prostate cancer.
- To determine the effects of targeting Cldn3/Cldn4 expression on prostate cancer cell growth, viability, and migration.
Main Methods:
- Human prostate cancer cell lines (PC3 and LNCaP) were utilized.
- Cells were transfected with small interfering RNAs (siRNAs) specific for Cldn3 or Cldn4.
- Protein levels, cell growth, viability, migration, and colony formation were assessed post-transfection.
Main Results:
- siRNA treatment led to an >85% decrease in Cldn3/Cldn4 protein levels.
- Prostate cancer cell growth decreased by 30-40%, and cell viability reduced by 60-65%.
- Cell migration was reduced, and colony formation decreased by 60-75% in siRNA-treated cells compared to controls.
Conclusions:
- Knockdown of Cldn3/Cldn4 significantly inhibits prostate cancer cell growth, survival, and migration.
- Claudins 3 and 4 represent promising molecular targets for therapeutic intervention in advanced prostate cancer.
- These findings highlight the potential of targeting Cldn3/Cldn4 for future prostate cancer therapies.
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