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Published on: September 8, 2017
Mechanical modulation of docetaxel-treated bladder cancer cells by various changes in cytoskeletal structures
Joanna Zemła1, Claude Verdier2, Marcin Luty1
1Institute of Nuclear Physics Polish Academy of Sciences, PL-31342, Krakow, Poland.
Abstract:
Cytoskeleton targeting agents are a group of chemotherapeutics used in the therapy of many types of cancer, such as breast, prostate, lung, bladder cancer, and others. At the same time, the assessment of the rheological properties of cancer cells is a relevant marker of their metastatic potential and therapeutic efficacy. For these reasons, understanding the interaction between the actin microfilament (MFs) network, microtubules (MTs), and so-called intermediate filaments (IFs) is crucial for the use of the rheological properties of cells as biomechanical markers. The current work compares the rheological properties of bladder cancer cells T24 and 5637, which differ in cytoskeletal composition, treated with a low dose of docetaxel (DTX) - a microtubule targeting agent (MTA). AFM revealed that 5637 cells stiffen over time when exposed to DTX, whereas changes in rheological properties of T24 cells are less pronounced, and both softening and stiffening of cells are observed. From immunostaining and Western blot analysis, we found that in addition to changes in the content and organization of MTs, reorganization of MFs and vimentin IFs also occurs. We show that both cell and nucleus morphology changes after DTX treatment. DTX treatment decreases and increases the migratory potential of 5637 and T24 cells, respectively. The current work shows that vimentin IFs modulate the nanomechanics of bladder cancer cells.
Insights
Docetaxel (DTX) alters bladder cancer cell mechanics by affecting cytoskeletal networks. Vimentin intermediate filaments play a key role in modulating these nanomechanical changes and cell migration potential.
Area of Science:
- Biophysics
- Cell Biology
- Cancer Research
Background:
- Cytoskeleton targeting agents are crucial cancer chemotherapeutics.
- Cell rheology is a marker for cancer metastasis and treatment efficacy.
- Understanding the interplay of actin, microtubules, and intermediate filaments is vital for cell biomechanics.
Purpose of the Study:
- To compare rheological properties of bladder cancer cells T24 and 5637 treated with docetaxel (DTX).
- To investigate the role of cytoskeletal composition in cellular response to DTX.
- To elucidate the contribution of vimentin intermediate filaments to cancer cell nanomechanics.
Main Methods:
- Atomic Force Microscopy (AFM) for rheological property assessment.
- Immunostaining and Western blot analysis for cytoskeletal component evaluation.
- Morphological analysis of cells and nuclei.
Main Results:
- DTX treatment caused differential stiffening in 5637 cells and varied rheological changes in T24 cells.
- DTX induced reorganization of microtubules, actin microfilaments, and vimentin intermediate filaments.
- DTX altered cell and nucleus morphology, decreasing migration in 5637 cells and increasing it in T24 cells.
Conclusions:
- Vimentin intermediate filaments significantly modulate the nanomechanics of bladder cancer cells.
- Differential cellular responses to DTX highlight the importance of cytoskeletal composition.
- Rheological properties influenced by cytoskeletal dynamics offer potential biomechanical markers for cancer therapy.
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