MDA-MB-231 breast cancer cells and their CSC population migrate towards low oxygen in a microfluidic gradient device

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Most cancer deaths are caused by secondary tumors formed through metastasis, yet due to our limited understanding of this process, prevention remains a major challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of metastases, but only little is known about their migratory behavior. Oxygen gradients in the tumor have been linked to directional migration of breast cancer cells. Here, we present a method to study the effect of oxygen gradients on the migratory behavior of breast CSCs using a microfluidic device. Our chip contains a chamber in which an oxygen gradient can be generated between hypoxic (<1%) and ambient (21%) conditions. We tracked the migration of CSCs obtained from MDA-MB-231 breast cancer cells, and found that their migration patterns do not differ from the average MDA-MB-231 population. Surprisingly, we found that the cells migrate towards low oxygen levels, in contrast with an earlier study. We hypothesize that in our device, migration is exclusively due to the pure oxygen gradient, whereas the effects of oxygen in earlier work were obscured by additional cues from the tumor microenvironment (e.g., nutrients and metabolites). These results open new research directions into the role of oxygen in directing cancer and CSC migration.
TaalEngels
Artikelnummer3047
Aantal pagina's15
TijdschriftInternational Journal of Molecular Sciences
Volume19
Nummer van het tijdschrift10
DOI's
StatusGepubliceerd - 6 okt 2018

Vingerafdruk

Lab-On-A-Chip Devices
multiple docking adapters
Neoplastic Stem Cells
stem cells
Stem cells
Microfluidics
breast
cancer
Cells
Breast Neoplasms
Oxygen
gradients
oxygen
Population
Tumors
tumors
metastasis
Neoplasms
Neoplasm Metastasis
Tumor Microenvironment

Trefwoorden

    Citeer dit

    @article{57973a7943254b5d9000dc94407a3907,
    title = "MDA-MB-231 breast cancer cells and their CSC population migrate towards low oxygen in a microfluidic gradient device",
    abstract = "Most cancer deaths are caused by secondary tumors formed through metastasis, yet due to our limited understanding of this process, prevention remains a major challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of metastases, but only little is known about their migratory behavior. Oxygen gradients in the tumor have been linked to directional migration of breast cancer cells. Here, we present a method to study the effect of oxygen gradients on the migratory behavior of breast CSCs using a microfluidic device. Our chip contains a chamber in which an oxygen gradient can be generated between hypoxic (<1{\%}) and ambient (21{\%}) conditions. We tracked the migration of CSCs obtained from MDA-MB-231 breast cancer cells, and found that their migration patterns do not differ from the average MDA-MB-231 population. Surprisingly, we found that the cells migrate towards low oxygen levels, in contrast with an earlier study. We hypothesize that in our device, migration is exclusively due to the pure oxygen gradient, whereas the effects of oxygen in earlier work were obscured by additional cues from the tumor microenvironment (e.g., nutrients and metabolites). These results open new research directions into the role of oxygen in directing cancer and CSC migration.",
    keywords = "Cancer Stem Cells, Tumor Microenvironment, Metastasis, Oxygen Gradient, Migration, Microfluidics",
    author = "J.J.F. Sleeboom and {den Toonder}, J.M.J. and C.M. Sahlgren",
    year = "2018",
    month = "10",
    day = "6",
    doi = "10.3390/ijms19103047",
    language = "English",
    volume = "19",
    journal = "International Journal of Molecular Sciences",
    issn = "1422-0067",
    publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
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    TY - JOUR

    T1 - MDA-MB-231 breast cancer cells and their CSC population migrate towards low oxygen in a microfluidic gradient device

    AU - Sleeboom,J.J.F.

    AU - den Toonder,J.M.J.

    AU - Sahlgren,C.M.

    PY - 2018/10/6

    Y1 - 2018/10/6

    N2 - Most cancer deaths are caused by secondary tumors formed through metastasis, yet due to our limited understanding of this process, prevention remains a major challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of metastases, but only little is known about their migratory behavior. Oxygen gradients in the tumor have been linked to directional migration of breast cancer cells. Here, we present a method to study the effect of oxygen gradients on the migratory behavior of breast CSCs using a microfluidic device. Our chip contains a chamber in which an oxygen gradient can be generated between hypoxic (<1%) and ambient (21%) conditions. We tracked the migration of CSCs obtained from MDA-MB-231 breast cancer cells, and found that their migration patterns do not differ from the average MDA-MB-231 population. Surprisingly, we found that the cells migrate towards low oxygen levels, in contrast with an earlier study. We hypothesize that in our device, migration is exclusively due to the pure oxygen gradient, whereas the effects of oxygen in earlier work were obscured by additional cues from the tumor microenvironment (e.g., nutrients and metabolites). These results open new research directions into the role of oxygen in directing cancer and CSC migration.

    AB - Most cancer deaths are caused by secondary tumors formed through metastasis, yet due to our limited understanding of this process, prevention remains a major challenge. Recently, cancer stem cells (CSCs) have been proposed as the source of metastases, but only little is known about their migratory behavior. Oxygen gradients in the tumor have been linked to directional migration of breast cancer cells. Here, we present a method to study the effect of oxygen gradients on the migratory behavior of breast CSCs using a microfluidic device. Our chip contains a chamber in which an oxygen gradient can be generated between hypoxic (<1%) and ambient (21%) conditions. We tracked the migration of CSCs obtained from MDA-MB-231 breast cancer cells, and found that their migration patterns do not differ from the average MDA-MB-231 population. Surprisingly, we found that the cells migrate towards low oxygen levels, in contrast with an earlier study. We hypothesize that in our device, migration is exclusively due to the pure oxygen gradient, whereas the effects of oxygen in earlier work were obscured by additional cues from the tumor microenvironment (e.g., nutrients and metabolites). These results open new research directions into the role of oxygen in directing cancer and CSC migration.

    KW - Cancer Stem Cells

    KW - Tumor Microenvironment

    KW - Metastasis

    KW - Oxygen Gradient

    KW - Migration

    KW - Microfluidics

    U2 - 10.3390/ijms19103047

    DO - 10.3390/ijms19103047

    M3 - Article

    VL - 19

    JO - International Journal of Molecular Sciences

    T2 - International Journal of Molecular Sciences

    JF - International Journal of Molecular Sciences

    SN - 1422-0067

    IS - 10

    M1 - 3047

    ER -