Comprehensive study on cellular morphologies, proliferation, motility, and epithelial–mesenchymal transition of breast cancer cells incubated on electrospun polymeric fiber substrates

Domura, Ryota; Sasaki, Rie; Okamoto, Masami; Hirano, Minoru; Kohda, Katsunori; Napiwocki, Brett N.; Turng, Lih Sheng

doi:10.1039/c7tb00207f

Cited by 23 publications

(19 citation statements)

References 72 publications

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“…This is presumably due to the colonization, which leads to an enhanced cell–cell contact via E-cadherin, following the less traction forces (contractility) generation and transmitted stresses to nucleus occurring [23]. …”

Section: Resultsmentioning

confidence: 99%

Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells

Domura

Sasaki

Ishikawa

et al. 2017

JFB

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The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (poly(l-lactic acid) and poly(ε-caprolactone), PLLA and PCL, respectively) as well as collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter (nucleus/cytoplasm area ratio) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC50) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

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Section: Resultsmentioning

confidence: 99%

Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells

Domura

Sasaki

Ishikawa

et al. 2017

JFB

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“…For the invasive MDA-MB-231 breast cancer cells in particular, increased proliferation has been noted for matrices of rigidities corresponding to the native tissue rigidities, where the differential rigidity response was related to Fyn kinase signaling [ 40 ]. Increased proliferation at 6 days of culture on stiff substrates for MDA-MB-231 and MCF-7 cells has also been linked to more stable focal adhesions and nuclear factor kappa-B (NF-κB) activation [ 41 ]. NF-κB is involved in tumor development including cell proliferation and apoptosis [ 42 ] and is regulated by actomyosin contractility [ 43 ] as well as by cell shape and the microenvironment stiffness in breast epithelial and tumor cells [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Morphological adaptations in breast cancer cells as a function of prolonged passaging on compliant substrates

et al. 2017

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Standard tissue culture practices involve propagating cells on tissue culture polystyrene (TCP) dishes, which are flat, 2-dimensional (2D) and orders of magnitude stiffer than most tissues in the body. Such simplified conditions lead to phenotypical cell changes and altered cell behaviors. Hence, much research has been focused on developing novel biomaterials and culture conditions that more closely emulate in vivo cell microenvironments. In particular, biomaterial stiffness has emerged as a key property that greatly affects cell behaviors such as adhesion, morphology, proliferation and motility among others. Here we ask whether cells that have been conditioned to TCP, would still show significant dependence on substrate stiffness if they are first pre-adapted to a more physiologically relevant environment. We used two commonly utilized breast cancer cell lines, namely MDA-MB-231 and MCF-7, and examined the effect of prolonged cell culturing on polyacrylamide substrates of varying compliance. We followed changes in cell adhesion, proliferation, shape factor, spreading area and spreading rate. After pre-adaptation, we noted diminished differences in cell behaviors when comparing between soft (1 kPa) and stiff (103 kPa) gels as well as rigid TCP control. Prolonged culturing of cells on complaint substrates further influenced responses of pre-adapted cells when transferred back to TCP. Our results have implications for the study of stiffness-dependent cell behaviors and indicate that cell pre-adaptation to the substrate needs consideration.

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“…These results are consistent with the levels of cell viability as described in section 3.3. As mentioned above, MCF-7 cells have more responsive to elrotinib than MDA-MB-231 cells [22] (Figure 9(c)). Noted that, erlotinib works more effectively to MDA-MB-231 cells incubated on PLLA substrates in comparison with PCL substrates.…”

Section: Effect Of Aligned Substrates With Stiffness On Drug Sensitivitymentioning

confidence: 79%

“…This is presumably due to the colonization, which leads to an enhanced cell-cell contact via E-cadherin, following the less traction forces (contractility) generation and transmitted stresses to nucleus occurring [22]. Figure 3 shows the optical densities of MDA-MB-231 and MCF-7 cells cultured on different substrates (polystyrene tissue culture plates (TCP), collagen coat, collagen gel) at different time interval (24, 48 and 96 h).…”

Section: Collagen Gel Collagen Coatmentioning

confidence: 99%

Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells

Domura¹,

Sasaki²,

Ishikawa³

et al. 2017

Preprint

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Abstract:The interpretation of the local microenvironment of extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (PLLA and PCL) and collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter of (Nuclear/Cytoplasm) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity (IC50) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

show abstract

Comprehensive study on cellular morphologies, proliferation, motility, and epithelial–mesenchymal transition of breast cancer cells incubated on electrospun polymeric fiber substrates

Abstract: Aligned fibers substrates caused elongation and alignment of the MDA-MB-231 cells along the fiber directionsviareducing the cell roundness and E-cadherin expression.

Cited by 23 publications

References 72 publications

Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells

Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells

Morphological adaptations in breast cancer cells as a function of prolonged passaging on compliant substrates

Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells

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