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Insights into the Steps of Breast Cancer-Brain Metastases Development: Tumor Cell Interactions with the Blood-Brain Barrier

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Insights into the Steps of Breast Cancer-Brain Metastases Development: Tumor Cell Interactions with the Blood-Brain Barrier. / Hamester, Fabienne; Stürken, Christine; Saygi, Ceren; Qi, Minyue; Legler, Karen; Gorzelanny, Christian; Robador, José R; Schmalfeldt, Barbara; Laakmann, Elena; Müller, Volkmar; Witzel, Isabell; Oliveira-Ferrer, Leticia.

In: INT J MOL SCI, Vol. 23, No. 3, 1900, 08.02.2022.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hamester, F, Stürken, C, Saygi, C, Qi, M, Legler, K, Gorzelanny, C, Robador, JR, Schmalfeldt, B, Laakmann, E, Müller, V, Witzel, I & Oliveira-Ferrer, L 2022, 'Insights into the Steps of Breast Cancer-Brain Metastases Development: Tumor Cell Interactions with the Blood-Brain Barrier', INT J MOL SCI, vol. 23, no. 3, 1900. https://doi.org/10.3390/ijms23031900

APA

Hamester, F., Stürken, C., Saygi, C., Qi, M., Legler, K., Gorzelanny, C., Robador, J. R., Schmalfeldt, B., Laakmann, E., Müller, V., Witzel, I., & Oliveira-Ferrer, L. (2022). Insights into the Steps of Breast Cancer-Brain Metastases Development: Tumor Cell Interactions with the Blood-Brain Barrier. INT J MOL SCI, 23(3), [1900]. https://doi.org/10.3390/ijms23031900

Vancouver

Hamester F, Stürken C, Saygi C, Qi M, Legler K, Gorzelanny C et al. Insights into the Steps of Breast Cancer-Brain Metastases Development: Tumor Cell Interactions with the Blood-Brain Barrier. INT J MOL SCI. 2022 Feb 8;23(3). 1900. https://doi.org/10.3390/ijms23031900

Bibtex

@article{feca57a8754c4cc6880267b108a0985c,
title = "Insights into the Steps of Breast Cancer-Brain Metastases Development: Tumor Cell Interactions with the Blood-Brain Barrier",
abstract = "Brain metastases (BM) represent a growing problem for breast cancer (BC) patients. Recent studies have demonstrated a strong impact of the BC molecular subtype on the incidence of BM development. This study explores the interaction between BC cells of different molecular subtypes and the blood-brain barrier (BBB). We compared the ability of BC cells of different molecular subtypes to overcome several steps (adhesion to the brain endothelium, disruption of the BBB, and invasion through the endothelial layer) during cerebral metastases formation, in vitro as well as in vivo. Further, the impact of these cells on the BBB was deciphered at the molecular level by transcriptome analysis of the triple-negative (TNBC) cells themselves as well as of hBMECs after cocultivation with BC cell secretomes. Compared to luminal BC cells, TNBC cells have a greater ability to influence the BBB in vitro and consequently develop BM in vivo. The brain-seeking subline and parental TNBC cells behaved similarly in terms of adhesion, whereas the first showed a stronger impact on the brain endothelium integrity and increased invasive ability. The comparative transcriptome revealed potential brain-metastatic-specific key regulators involved in the aforementioned processes, e.g., the angiogenesis-related factors TNXIP and CXCL1. In addition, the transcriptomes of the two TNBC cell lines strongly differed in certain angiogenesis-associated factors and in several genes related to cell migration and invasion. Based on the present study, we hypothesize that the tumor cell's ability to disrupt the BBB via angiogenesis activation, together with increased cellular motility, is required for BC cells to overcome the BBB and develop brain metastases.",
keywords = "Animals, Blood-Brain Barrier, Brain Neoplasms/genetics, Breast Neoplasms/genetics, Cell Communication, Cell Line, Tumor, Cell Movement, Female, Gene Expression Profiling/methods, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, MCF-7 Cells, Mice, Neoplasm Transplantation",
author = "Fabienne Hamester and Christine St{\"u}rken and Ceren Saygi and Minyue Qi and Karen Legler and Christian Gorzelanny and Robador, {Jos{\'e} R} and Barbara Schmalfeldt and Elena Laakmann and Volkmar M{\"u}ller and Isabell Witzel and Leticia Oliveira-Ferrer",
year = "2022",
month = feb,
day = "8",
doi = "10.3390/ijms23031900",
language = "English",
volume = "23",
journal = "INT J MOL SCI",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "3",

}

RIS

TY - JOUR

T1 - Insights into the Steps of Breast Cancer-Brain Metastases Development: Tumor Cell Interactions with the Blood-Brain Barrier

AU - Hamester, Fabienne

AU - Stürken, Christine

AU - Saygi, Ceren

AU - Qi, Minyue

AU - Legler, Karen

AU - Gorzelanny, Christian

AU - Robador, José R

AU - Schmalfeldt, Barbara

AU - Laakmann, Elena

AU - Müller, Volkmar

AU - Witzel, Isabell

AU - Oliveira-Ferrer, Leticia

PY - 2022/2/8

Y1 - 2022/2/8

N2 - Brain metastases (BM) represent a growing problem for breast cancer (BC) patients. Recent studies have demonstrated a strong impact of the BC molecular subtype on the incidence of BM development. This study explores the interaction between BC cells of different molecular subtypes and the blood-brain barrier (BBB). We compared the ability of BC cells of different molecular subtypes to overcome several steps (adhesion to the brain endothelium, disruption of the BBB, and invasion through the endothelial layer) during cerebral metastases formation, in vitro as well as in vivo. Further, the impact of these cells on the BBB was deciphered at the molecular level by transcriptome analysis of the triple-negative (TNBC) cells themselves as well as of hBMECs after cocultivation with BC cell secretomes. Compared to luminal BC cells, TNBC cells have a greater ability to influence the BBB in vitro and consequently develop BM in vivo. The brain-seeking subline and parental TNBC cells behaved similarly in terms of adhesion, whereas the first showed a stronger impact on the brain endothelium integrity and increased invasive ability. The comparative transcriptome revealed potential brain-metastatic-specific key regulators involved in the aforementioned processes, e.g., the angiogenesis-related factors TNXIP and CXCL1. In addition, the transcriptomes of the two TNBC cell lines strongly differed in certain angiogenesis-associated factors and in several genes related to cell migration and invasion. Based on the present study, we hypothesize that the tumor cell's ability to disrupt the BBB via angiogenesis activation, together with increased cellular motility, is required for BC cells to overcome the BBB and develop brain metastases.

AB - Brain metastases (BM) represent a growing problem for breast cancer (BC) patients. Recent studies have demonstrated a strong impact of the BC molecular subtype on the incidence of BM development. This study explores the interaction between BC cells of different molecular subtypes and the blood-brain barrier (BBB). We compared the ability of BC cells of different molecular subtypes to overcome several steps (adhesion to the brain endothelium, disruption of the BBB, and invasion through the endothelial layer) during cerebral metastases formation, in vitro as well as in vivo. Further, the impact of these cells on the BBB was deciphered at the molecular level by transcriptome analysis of the triple-negative (TNBC) cells themselves as well as of hBMECs after cocultivation with BC cell secretomes. Compared to luminal BC cells, TNBC cells have a greater ability to influence the BBB in vitro and consequently develop BM in vivo. The brain-seeking subline and parental TNBC cells behaved similarly in terms of adhesion, whereas the first showed a stronger impact on the brain endothelium integrity and increased invasive ability. The comparative transcriptome revealed potential brain-metastatic-specific key regulators involved in the aforementioned processes, e.g., the angiogenesis-related factors TNXIP and CXCL1. In addition, the transcriptomes of the two TNBC cell lines strongly differed in certain angiogenesis-associated factors and in several genes related to cell migration and invasion. Based on the present study, we hypothesize that the tumor cell's ability to disrupt the BBB via angiogenesis activation, together with increased cellular motility, is required for BC cells to overcome the BBB and develop brain metastases.

KW - Animals

KW - Blood-Brain Barrier

KW - Brain Neoplasms/genetics

KW - Breast Neoplasms/genetics

KW - Cell Communication

KW - Cell Line, Tumor

KW - Cell Movement

KW - Female

KW - Gene Expression Profiling/methods

KW - Gene Expression Regulation, Neoplastic

KW - Gene Regulatory Networks

KW - Humans

KW - MCF-7 Cells

KW - Mice

KW - Neoplasm Transplantation

U2 - 10.3390/ijms23031900

DO - 10.3390/ijms23031900

M3 - SCORING: Journal article

C2 - 35163822

VL - 23

JO - INT J MOL SCI

JF - INT J MOL SCI

SN - 1661-6596

IS - 3

M1 - 1900

ER -