Blood–Brain Barrier Remodeling in an Organ‐on‐a‐Chip Device Showing Dkk1 to be a Regulator of Early Metastasis
Brain metastases are the most lethal progression events, in part because the biological processes underpinning brain metastases are poorly understood. There is a paucity of realistic models of metastasis, as current in vivo murine models are slow to manifest metastasis. Metabolic and secretory modul...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley-VCH
2023-04-01
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| Series: | Advanced NanoBiomed Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/anbr.202200036 |
| _version_ | 1827897493341339648 |
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| author | Trisha M. Westerhof Benjamin A. Yang Nathan M. Merrill Joel A. Yates Megan Altemus Liam Russell Anna J. Miller Liwei Bao Zhifen Wu Peter J. Ulintz Carlos A. Aguilar Aki Morikawa Maria G. Castro Sofia D. Merajver Christopher R. Oliver |
| author_facet | Trisha M. Westerhof Benjamin A. Yang Nathan M. Merrill Joel A. Yates Megan Altemus Liam Russell Anna J. Miller Liwei Bao Zhifen Wu Peter J. Ulintz Carlos A. Aguilar Aki Morikawa Maria G. Castro Sofia D. Merajver Christopher R. Oliver |
| author_sort | Trisha M. Westerhof |
| collection | DOAJ |
| description | Brain metastases are the most lethal progression events, in part because the biological processes underpinning brain metastases are poorly understood. There is a paucity of realistic models of metastasis, as current in vivo murine models are slow to manifest metastasis. Metabolic and secretory modulators of brain metastases utilizing two models consisting of in vitro microfluidic devices are delineated: 1) a blood–brain niche (BBN) chip that recapitulates the blood–brain‐ barrier and niche; and 2) a migration chip that assesses cell migration. Secretory cues provided by the brain niche that attract metastatic cancer cells to colonize the brain niche region are reported. Astrocytic Dkk‐1 is increased in response to brain‐seeking breast cancer cells and stimulates cancer cell migration. Brain metastatic cancer cells under Dkk‐1 stimulation increase gene expression of FGF‐13 and PLCB1. Further, extracellular Dkk‐1 modulates cancer cell migration upon entering the brain niche. |
| first_indexed | 2024-03-12T22:49:54Z |
| format | Article |
| id | doaj.art-35ecd751082c4a2199f6c3b510c3f638 |
| institution | Directory Open Access Journal |
| issn | 2699-9307 |
| language | English |
| last_indexed | 2024-03-12T22:49:54Z |
| publishDate | 2023-04-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Advanced NanoBiomed Research |
| spelling | doaj.art-35ecd751082c4a2199f6c3b510c3f6382023-07-20T12:56:21ZengWiley-VCHAdvanced NanoBiomed Research2699-93072023-04-0134n/an/a10.1002/anbr.202200036Blood–Brain Barrier Remodeling in an Organ‐on‐a‐Chip Device Showing Dkk1 to be a Regulator of Early MetastasisTrisha M. Westerhof0Benjamin A. Yang1Nathan M. Merrill2Joel A. Yates3Megan Altemus4Liam Russell5Anna J. Miller6Liwei Bao7Zhifen Wu8Peter J. Ulintz9Carlos A. Aguilar10Aki Morikawa11Maria G. Castro12Sofia D. Merajver13Christopher R. Oliver14Michigan Medicine Department of Internal Medicine Division of Hematology/Oncology University of Michigan Medical School Ann Arbor MI 48109 USASchool of Engineering Department of Biomedical Engineering University of Michigan Ann Arbor MI 48109 USAMichigan Medicine Department of Internal Medicine Division of Hematology/Oncology University of Michigan Medical School Ann Arbor MI 48109 USAMichigan Medicine Department of Internal Medicine Division of Hematology/Oncology University of Michigan Medical School Ann Arbor MI 48109 USAMichigan Medicine Department of Internal Medicine Division of Hematology/Oncology University of Michigan Medical School Ann Arbor MI 48109 USASchool of Engineering Department of Biomedical Engineering University of Michigan Ann Arbor MI 48109 USASchool of Engineering Department of Biomedical Engineering University of Michigan Ann Arbor MI 48109 USAMichigan Medicine Department of Internal Medicine Division of Hematology/Oncology University of Michigan Medical School Ann Arbor MI 48109 USAMichigan Medicine Department of Internal Medicine Division of Hematology/Oncology University of Michigan Medical School Ann Arbor MI 48109 USAMichigan Medicine Department of Internal Medicine Division of Hematology/Oncology University of Michigan Medical School Ann Arbor MI 48109 USASchool of Engineering Department of Biomedical Engineering University of Michigan Ann Arbor MI 48109 USAMichigan Medicine Department of Internal Medicine Division of Hematology/Oncology University of Michigan Medical School Ann Arbor MI 48109 USAMichigan Medicine Department of Neurosurgery University of Michigan Ann Arbor MI 48109 USAMichigan Medicine Department of Internal Medicine Division of Hematology/Oncology University of Michigan Medical School Ann Arbor MI 48109 USAMichigan Medicine Department of Internal Medicine Division of Hematology/Oncology University of Michigan Medical School Ann Arbor MI 48109 USABrain metastases are the most lethal progression events, in part because the biological processes underpinning brain metastases are poorly understood. There is a paucity of realistic models of metastasis, as current in vivo murine models are slow to manifest metastasis. Metabolic and secretory modulators of brain metastases utilizing two models consisting of in vitro microfluidic devices are delineated: 1) a blood–brain niche (BBN) chip that recapitulates the blood–brain‐ barrier and niche; and 2) a migration chip that assesses cell migration. Secretory cues provided by the brain niche that attract metastatic cancer cells to colonize the brain niche region are reported. Astrocytic Dkk‐1 is increased in response to brain‐seeking breast cancer cells and stimulates cancer cell migration. Brain metastatic cancer cells under Dkk‐1 stimulation increase gene expression of FGF‐13 and PLCB1. Further, extracellular Dkk‐1 modulates cancer cell migration upon entering the brain niche.https://doi.org/10.1002/anbr.202200036blood–brain barriercancerdkk-1metastasismicroenvironmentsmicrofluidic |
| spellingShingle | Trisha M. Westerhof Benjamin A. Yang Nathan M. Merrill Joel A. Yates Megan Altemus Liam Russell Anna J. Miller Liwei Bao Zhifen Wu Peter J. Ulintz Carlos A. Aguilar Aki Morikawa Maria G. Castro Sofia D. Merajver Christopher R. Oliver Blood–Brain Barrier Remodeling in an Organ‐on‐a‐Chip Device Showing Dkk1 to be a Regulator of Early Metastasis Advanced NanoBiomed Research blood–brain barrier cancer dkk-1 metastasis microenvironments microfluidic |
| title | Blood–Brain Barrier Remodeling in an Organ‐on‐a‐Chip Device Showing Dkk1 to be a Regulator of Early Metastasis |
| title_full | Blood–Brain Barrier Remodeling in an Organ‐on‐a‐Chip Device Showing Dkk1 to be a Regulator of Early Metastasis |
| title_fullStr | Blood–Brain Barrier Remodeling in an Organ‐on‐a‐Chip Device Showing Dkk1 to be a Regulator of Early Metastasis |
| title_full_unstemmed | Blood–Brain Barrier Remodeling in an Organ‐on‐a‐Chip Device Showing Dkk1 to be a Regulator of Early Metastasis |
| title_short | Blood–Brain Barrier Remodeling in an Organ‐on‐a‐Chip Device Showing Dkk1 to be a Regulator of Early Metastasis |
| title_sort | blood brain barrier remodeling in an organ on a chip device showing dkk1 to be a regulator of early metastasis |
| topic | blood–brain barrier cancer dkk-1 metastasis microenvironments microfluidic |
| url | https://doi.org/10.1002/anbr.202200036 |
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