Reactive astrocytic S1P3 signaling modulates the blood–tumor barrier in brain metastases

Gril, Brunilde; Paranjape, Anurag N.; Woditschka, Stephan; Hua, Emily; Dolan, Emma; Hanson, Jeffrey; Wu, Xiaolin; Kloc, Wojciech; Iżycka-Świeszewska, Ewa; Duchnowska, Renata; Pęksa, Rafał; Biernat, Wojciech; Jassem, Jacek; Nayyar, Naema; Brastianos, Priscilla K.; Hall, O. Morgan; Peer, Cody J.; Figg, William D.; Pauly, Gary T.; Robinson, Christina M.; Difilippantonio, Simone; Bialecki, Emilie; Métellus, Philippe; Schneider, Joel P.; Steeg, Patricia S.

doi:10.1038/s41467-018-05030-w

Cited by 94 publications

(80 citation statements)

References 67 publications

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“…[ 3 ] The tight junction of complexes between adjacent endothelial cells further strengthens the functional integrity of BBB, which strictly monitors and controls the import and export of different substances of the brain. [ 4 ] It is reported that nearly 98% of small‐molecule drugs or contrast agents and most macromolecular drugs are routinely excluded from the brain, which makes the treatment and imaging of brain tumors extremely difficult. [ 5,6 ] Although the tight junctions of BBB at the late stage of brain tumors are disrupted to permit drug penetration into brain, the drug concentration in tumor sites is not sufficient to reach the therapeutic level.…”

Section: Introductionmentioning

confidence: 99%

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

Wang

et al. 2020

Adv Funct Materials

144

120

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Glioblastoma multiforme is one of the most fatal intracranial tumors with no effective treatment. The drug concentration in tumor sites is usually insufficient to reach therapeutic levels, due to poor blood–brain‐barrier (BBB) permeability and short biological half‐life. Inspired by the proneness of those malignant tumors to brain metastasis, a brain metastatic tumor cell membrane‐coated nanocarrier with core–shell structure is constructed to cross BBB for imaging and photothermal therapy of early brain tumors. The cell membranes as the shell are extracted from different metastatic tumor cells, which endow the nanoparticles with BBB‐crossing ability and long circulation. Indocyanine green (ICG)‐loaded polymeric nanoparticle as the core allows fluorescence imaging and phototherapy of brain tumors. The as‐prepared biomimetic nanoparticles display superb BBB penetration and effective suppression of tumor growth. These findings suggest the biomimetic nanotechnology provides a new insight for the design of BBB‐crossing nanomaterials and is promising to treat brain diseases.

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Section: Introductionmentioning

confidence: 99%

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

Wang

et al. 2020

Adv Funct Materials

144

120

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“…Interestingly, the BBB protects the normal brain, looses its permeability partially or hetrogenously, and transforms into a blood-tumor barrier (BTB) which enhances the accessibily of therapeutic drugs to some extent, but not completly [14]. However the therapeutic role of BTB permeability is not well defined.…”

Section: Introductionmentioning

confidence: 99%

“…However the therapeutic role of BTB permeability is not well defined. Smith et al, demonstrated that BTB limits the uptake of chemotherapeutic drugs for BC, such as doxorubicin and paclitaxel into the brain relative to other organs [14,15], suggesting limitations of BTB for the complete response of these drugs.…”

Section: Introductionmentioning

confidence: 99%

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

et al. 2020

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Brain metastasis (BM) predominantly occurs in triple-negative (TN) and epidermal growth factor 2 (HER2)-positive breast cancer (BC) patients, and currently, there is an unmet need for the treatment of these patients. BM is a complex process that is regulated by the formation of a metastatic niche. A better understanding of the brain metastatic processes and the crosstalk between cancer cells and brain microenvironment is essential for designing a novel therapeutic approach. In this context, the aberrant expression of miRNA has been shown to be associated with BM. These non-coding RNAs/miRNAs regulate metastasis through modulating the formation of a metastatic niche and metabolic reprogramming via regulation of their target genes. However, the role of miRNA in breast cancer brain metastasis (BCBM) is poorly explored. Thus, identification and understanding of miRNAs in the pathobiology of BCBM may identify a novel candidate miRNA for the early diagnosis and prevention of this devastating process. In this review, we focus on understanding the role of candidate miRNAs in the regulation of BC brain metastatic processes as well as designing novel miRNA-based therapeutic strategies for BCBM.Keywords: Breast cancer brain metastasis, miRNA, Brain tumor microenvironment, Blood-brain barrier, CNS metastasis

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“…Many of the cytokines/chemokines we identified have previously been reported to be involved in regulating the blood-tumor-barrier, e.g., GRO-α, ICAM-1, IL-6, IL-8, GM-CSF, and CCL5 [58]. Others have found that these proteins also have an impact on BBB integrity and/or facilitate BBB transmigration, e.g., ICAM-1, GM-CSF, CCL5 [55][56][57][58]. Additionally, IL-8 was shown to bind to Sdc1, thereby facilitating leukocyte transendothelial migration [46].…”

Section: Discussionmentioning

confidence: 90%

Syndecan-1 facilitates breast cancer metastasis to the brain

Sayyad

Puchalapalli

Vergara

et al. 2019

Preprint

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Purpose: Although survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis. Methods:To assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triplenegative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood-brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 promotes brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 is silenced.Results: Silencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that silencing of Sdc1 expression had no effect on attachment of breast cancer cells to brain endothelial cells or astrocytes, but migration across the BBB was reduced as well as adhesion to the perivascular regions of the brain. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines/chemokines, which may influence the BBB. Conclusions:Taken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.

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Reactive astrocytic S1P3 signaling modulates the blood–tumor barrier in brain metastases

Cited by 94 publications

References 67 publications

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

Syndecan-1 facilitates breast cancer metastasis to the brain

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