Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity

combined application of AFM and modulated Raman spectroscopy

Elisabetta Canetta, Andrew Riches, Eva Borger, Simon Herrington, Kishan Dholakia, Ashok K. Adya (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    29 Citations (Scopus)

    Abstract

    Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates bladder tumour cells to be more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterised by higher protein contents. AFM studies revealed decrease in the lateral dimensions and increase in thickness of cancer cells compared to normal cells which authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity, and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83%, 98%, and 95%) and sensitivity (97%, 93%, and 98%). Such single cell-level studies could have a pivotal impact in the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance.
    Original languageEnglish
    Pages (from-to)2043-2055
    JournalActa Biomaterialia
    Volume10
    Issue number5
    Early online date7 Jan 2014
    DOIs
    Publication statusPublished - May 2014

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    Raman Spectrum Analysis
    Atomic Force Microscopy
    Urinary Bladder Neoplasms
    Raman spectroscopy
    Atomic force microscopy
    Cells
    Sensitivity and Specificity
    Tumors
    Elasticity
    Adhesion
    Cell membranes
    Lipids
    Raman scattering
    Screening
    DNA
    Elastic moduli
    Proteins
    Elastic Modulus
    Dermatoglyphics

    Keywords

    • atomic force microscopy
    • Modulated Raman spectroscopy
    • Bladder cancer
    • Cytoskeleton organization
    • Cell mechanics

    Cite this

    Canetta, Elisabetta ; Riches, Andrew ; Borger, Eva ; Herrington, Simon ; Dholakia, Kishan ; Adya, Ashok K. / Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity : combined application of AFM and modulated Raman spectroscopy. In: Acta Biomaterialia. 2014 ; Vol. 10, No. 5. pp. 2043-2055.
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    abstract = "Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates bladder tumour cells to be more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterised by higher protein contents. AFM studies revealed decrease in the lateral dimensions and increase in thickness of cancer cells compared to normal cells which authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity, and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83{\%}, 98{\%}, and 95{\%}) and sensitivity (97{\%}, 93{\%}, and 98{\%}). Such single cell-level studies could have a pivotal impact in the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance.",
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    Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity : combined application of AFM and modulated Raman spectroscopy. / Canetta, Elisabetta; Riches, Andrew; Borger, Eva; Herrington, Simon; Dholakia, Kishan; Adya, Ashok K. (Lead / Corresponding author).

    In: Acta Biomaterialia, Vol. 10, No. 5, 05.2014, p. 2043-2055.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity

    T2 - combined application of AFM and modulated Raman spectroscopy

    AU - Canetta, Elisabetta

    AU - Riches, Andrew

    AU - Borger, Eva

    AU - Herrington, Simon

    AU - Dholakia, Kishan

    AU - Adya, Ashok K.

    N1 - Copyright © 2013. Published by Elsevier Ltd.

    PY - 2014/5

    Y1 - 2014/5

    N2 - Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates bladder tumour cells to be more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterised by higher protein contents. AFM studies revealed decrease in the lateral dimensions and increase in thickness of cancer cells compared to normal cells which authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity, and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83%, 98%, and 95%) and sensitivity (97%, 93%, and 98%). Such single cell-level studies could have a pivotal impact in the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance.

    AB - Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates bladder tumour cells to be more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterised by higher protein contents. AFM studies revealed decrease in the lateral dimensions and increase in thickness of cancer cells compared to normal cells which authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity, and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83%, 98%, and 95%) and sensitivity (97%, 93%, and 98%). Such single cell-level studies could have a pivotal impact in the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance.

    KW - atomic force microscopy

    KW - Modulated Raman spectroscopy

    KW - Bladder cancer

    KW - Cytoskeleton organization

    KW - Cell mechanics

    U2 - 10.1016/j.actbio.2013.12.057

    DO - 10.1016/j.actbio.2013.12.057

    M3 - Article

    VL - 10

    SP - 2043

    EP - 2055

    JO - Acta Biomaterialia

    JF - Acta Biomaterialia

    SN - 1742-7061

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    ER -